巴西专利BR112013016671B1 PLATE WITH NEBULIZING OPENING, VIBRATING MESH OF THE NEBULIZING TYPE AND METHOD FOR THE MANUFACTURIN

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专利摘要:
nebulizer opening plate, nebulizer-type vibrating mesh and method for making said plate, the present invention relates, in one embodiment, to a method for the manufacture of an opening plate that includes the deposition of a release layer of seed above a substrate, the application of a first patterned photolithography mask above the releasable seed layer, the first patterned photolithography mask having a negative pattern for a desired opening pattern, the plating of a first material above the exposed portions of the layer of releasable seeds and defined by the first mask, the application of a second photolithography mask above the first material, the second photolithography mask having a negative pattern in relation to a first cavity, the galvanization of a second material above the exposed portions of the first material and defined by the second mask, the removal of both masks and the stripping of the seed layer releasable to release the first material and the second material. the first and second material form an opening plate for use in dispersing a liquid. other opening plates and methods of producing opening plates are described according to other modalities.
公开号:BR112013016671B1
申请号:R112013016671-1
申请日:2011-12-23
公开日:2020-12-15
发明作者:Hong Xu
申请人:Stamford Devices Ltd；
IPC主号:

专利说明:

FIELD OF THE INVENTION
[001] The present invention relates to liquid nebulizers, and more specifically, to a plate with opening for such liquid nebulizers capable of aerosol dispensing of liquid formulations that have a controlled liquid drop size suitable for dispensing lung medicine. The invention also relates to the formation and use of open plates used to produce such aerosols. BACKGROUND
[002] In drug delivery applications, especially drug delivery to a patient's pulmonary system, liquid nebulizers are advantageous in that they are capable of delivering a fine aerosol mist to a patient. Such nebulizer devices aim to ensure a drop size and / or flow rate and / or velocity of the expelled drops to maximize distribution to the target portion of the pulmonary system, such as the deep lung.
[003] Some liquid nebulizers use a perforated plate, such as an opening plate (AP), mesh plate or vibrating plate, through which a liquid is forced in order to distribute a fine aerosol mist. In particular, liquid nebulizers of the vibrating mesh type are advantageous over other aerosol forming devices, such as jet nebulizers or ultrasonic nebulizers, in that they are capable of delivering a fine aerosol mist comprising a droplet size and drop size range suitable for delivery to the lung and are thus able to do this with relatively high efficiency and reliability. Such vibrating mesh nebulizers can advantageously be small, do not require high and / or external energy sources and do not introduce foreign gases into the patient's pulmonary system.
[004] Aperture plates manufactured for delivery to the lung of a liquid drug are often developed to have an aperture size that produces drops (also often referred to as particles) in the size range of about 1-6 μm. Conveniently, the opening plate can be provided with at least about 1,000 openings so that a volume of liquid in the range of about 4-30 μL can be produced within less than one second. In this way, a sufficient dosage can be dispersed. A plaque opening size of about 1-6 μm is useful because this particle size range provides an aerosol droplet deposition profile into the pulmonary system. More specifically, a size range of about 1-4 μm is useful because this particle size range provides an aerosol droplet deposition profile into the deep lung (comprising the bronchi and bronchioles, and sometimes referred to as the pulmonary region), with a higher effective dose distributed and concomitant therapeutic benefits. A particle size range greater than 6 μm can decrease the appropriate dispersion of the liquid into the lung region of the lung. Therefore, providing an appropriate aperture size range and controlling the aperture size distribution and thus the size distribution of liquid droplets is a problem in this industry. The development of a low-cost manufacturing process for the manufacture of open slabs in a consistent and reliable manner that has the appropriate opening sizes has been a challenge for the galvanizing technology commonly used for the production of slotted plates.
[005] Galvanization is a well-established coating technology so it has been widely used in the inkjet printing industry. Such devices usually have openings of greater geometry (about 10 μm or larger, in some examples). In a typical galvanizing process, a metal forming process is used to form thin parts through galvanizing on a base form, referred to as a mandrel. In a basic galvanizing process, an electrolytic bath is used to deposit a galvanizable metal on a standardized conductive surface, such as metallized glass (that is, deposited with a thin layer of metal) or stainless steel. Once the coated material has been constructed to a desirable thickness, the galvanized part is removed from the master substrate. This process ensures adequate reproducibility of the master substrate and, therefore, allows production with good repeatability and process control for openings of greater geometry (greater than about 10 μm). The mandrel is usually made of a conductive material, such as stainless steel. The object being galvanized can be a permanent part of the final product or it can be temporary, and removed later, leaving only the metal shape, that is, "the electroform".
[006] The galvanizing process is, however, disadvantageous in many aspects. Galvanization is very susceptible to imperfections and defects in the surface of the mandrel (for example, a supporting substrate surface) adversely affect the quality of a resulting open plate. As a result, high manufacturing yields and process consistency have remained elusive. A typical manufacturing yield for an open plate is around 30% and an assembly line inspection downstream of 100% may be required due to process variability.
[007] A cross-sectional view of a galvanized plate with an opening and a typical process flow are shown in figure 1A and figure 1B, respectively, according to the prior art. Conventionally, as shown in Figure 1A, an opening plate 102 is formed by the three-dimensional growth of the coating material over a variety of dome-shaped patterns 104 with specific diameter and spacing. The dome pattern 104 is lithographically standardized and then treated with heating over a stainless steel mandrel. The dome-shaped structure 104 acts only as an insulating layer for the subsequent coating, preventing correct and precise control of the opening geometry. The diameter and height of the dome-shaped structure 104 determines the approximate opening size 106 and the shape of the opening plates 102 produced through this process. The spacing or level between dome-shaped structures 104 is a determining factor in the final thickness of the plate with opening 102 due to the opening size 106 being determined by the coating time, that is, a longer coating time results in an opening size. 106 smaller. As a result, the density of the opening plate hole for a galvanized plate with conventional opening 102 is fixed for any given plate thickness. Because the flow rate is proportional to the opening density (or hole) of the opening plate, limiting the density of the galvanizing hole requires an increase in the diameter of the opening plate in order to distribute a higher flow rate. "Opening density" means the number of openings per square unit of open plate, as well as the number of openings per mm2. This has a significantly negative impact on manufacturing costs and manufacturing yield, for example, costs may be higher and yields may be lower. In addition, especially in medical applications, it is often preferable to minimize the diameter of an opening plate so that the entire device is as small as possible, for positioning and space requirements and to minimize energy consumption.
[008] Another limiting factor in the galvanization of the prior art is the control of opening size. As shown in figures 2A-2D, in order to achieve a smaller opening 202, the risk of blocking the opening plate hole increases considerably (due to a diffusion limiting factor near the conical opening area). Three-dimensional growth has both horizontal linear growth rH and vertical vertical growth rL. In the larger aperture size 202 (typically greater than about 10 µm), there is approximately a linear relationship between the horizontal growth rH and the vertical growth rL which allows the opening size 202 to be relatively well controlled. However, once aperture size 202 reaches a smaller dimension, linearity no longer occurs and controlling aperture size 202 becomes difficult. This non-linearity typically starts at aperture sizes of about 10 μm or smaller, such as less than about 9 μm or 8 μm or 7 μm or 6 μm. As can be seen in figures 2A-2D, the longer the growth time, as indicated by the time value (t) in each figure, the thicker the layer 204 becomes and the smaller the corresponding opening 202 becomes. Because the thickness 204 and the opening size 202 are interrelated during three-dimensional growth, the coating conditions must be monitored and modified during the coating process if it is desired to obtain the final opening size 202 and this is not always successful. successful. In some cases, As shown in figure 2D, the growth of the opening plate may fail due to the layer having grown too large, which causes the openings 202 to close. It is well known in the art that coating thickness 204 can vary, sometimes over 10%, across the coating layer due to limits inherent in process technology. Again, this makes it very difficult to control the final thickness of the opening plate 204 and opening size 202. SUMMARY
[009] According to one or more modalities, a method for the manufacture of an opening plate includes the deposition of a release layer of seed on a substrate, the application of a first standardized photolithography mask over the release layer of seed, the first patterned photolithography mask has a negative pattern for a desired opening pattern, the galvanization of a first material on exposed portions of the releasable seed layer and limited by the first mask, the application of a second photolithography mask on the first material, the second photolithography mask has a negative pattern for a first cavity, the galvanization of the second material on the exposed portions of the first material and limited by the second mask, the removal of both masks, and the stripping of the release layer of seed to release the first material and the second material. The first material and the second material form an opening plate for use in dispersing liquids.
[010] According to another modality, a plate with opening for use in the dispersion of liquids includes a first material that has a variety of openings, the first material has a characteristic of being formed through a photolithography process, a second material on the first material, the second material has a first cavity over the variety of openings in the first material, in which the second material has a characteristic of being formed through a photolitrography process. The first material and the second material form an opening plate.
[011] In yet another modality, a plate with an opening adapted for use in the dispersion of liquids produced by a process that includes the steps of: a) depositing a layer of releasable seed on a substrate, b) applying the first photolithography mask standardized on the release layer, the first standardized photolithography mask has a negative pattern for a desired opening pattern, c) the galvanization of a first material on the exposed portions of the release layer and limited by the first mask forming a structure substantially planar that has a variety of openings through it, d) the application of a second photolithography mask over the first material, the second photolithography mask has a negative pattern for a first cavity, in which the first cavity is positioned above the variety of openings, e) the galvanization of a second material on the exposed portions of the first material ial and limited by the second mask, f) removing both masks, and g) stripping the release layer of seed to release the first material and the second material.
[012] Other aspects and modalities of the present invention will become apparent from the following detailed description which, when taken in conjunction with the drawings, illustrates, by way of example, the principles of the invention. BRIEF DESCRIPTION OF THE DRAWINGS
[013] Figure 1A shows a schematic representation of the profile of a plate with an opening according to the prior art.
[014] Figure 1B shows a flowchart of a method of producing a plate with an opening according to the prior art.
[015] Figures 2A-2D demonstrate schematic representations of the profile during various growth stages of open plate growth, according to the prior art.
[016] Figures 3A-3B demonstrate a cross-sectional view and a top view, respectively, of an opening plate, according to an embodiment.
[017] Figures 4A-4B demonstrate a cross-sectional view and a top view, respectively, of an opening plate, according to an embodiment.
[018] Figure 5A shows a scanning electron microscope image, in a top-down view, of an opening plate, according to one modality.
[019] Figure 5B shows a scanning electron microscope image, in a top-down view, of an opening plate, according to one modality.
[020] Figure 6 shows a flow chart of a method of producing a plate with an opening according to a modality.
[021] Figures 7A-7L demonstrate various stages of forming a plate with an opening according to a modality.
[022] Figure 8A is a cross-sectional schematic representation of a nebulizer including an opening plate, according to an embodiment.
[023] Figure 8B is a schematic cross-sectional detail of the nebulizer shown in figure 8A, according to one modality. DETAILED DESCRIPTION
[024] The following description is made for the purpose of illustrating the general principles of the present invention and is not intended to limit the inventive concepts claimed here. In addition, the particular features described here can be used in combination with other features described in each of the various possible combinations and permutations.
[025] Unless otherwise specifically defined here, all terms should be considered in their broadest interpretations, including meanings implied from the specification, as well as the meanings understood by those versed in the technique and / or as defined in dictionaries , treaties, etc.
[026] As used herein, the term "liquid" can refer to a single-phase solution, a multi-phase solution, an emulsion or nanosuspension.
[027] As used herein, the term "cylinder" (and "cylindrical") refer to a geometric figure comprising a section of a circular cylinder; However, unless clarified by the context, other cross-sectional shapes may comprise the cylinders referred to here. Furthermore, the radius of the cylinder does not necessarily have to be uniform throughout the cylindrical shape, but may, in some embodiments, vary as from the top to the bottom to result in a certain degree of taper.
[028] It should also be noted that, as used in the specification and appended claims, the singular forms "um", "uma" "o" and "a" include the plural unless otherwise specified.
[029] According to a general modality, a method for the manufacture of an opening plate includes the deposition of a release layer of seed on a substrate, the application of the first standardized photolithography mask over the release layer, the first standardized photolithography mask has a negative pattern for a desired opening pattern, the galvanization of a first material above exposed portions of the releasable seed layer and limited by the first mask, the application of a second photolithography mask on the first material, the second photolithography mask has a negative pattern for a first cavity, the galvanization of a second material on the exposed portions of the first material and limited by the second mask, the removal of both masks, and a pickling of the release layer of seed to release the first material and the second material. The first material and the second material form an opening plate for use in dispersing liquids.
[030] According to another general modality, a plate with opening for use in the dispersion of liquids includes a first material that has a variety of openings, the first material has a characteristic of being formed through a photolithography process, a second material above the first material, the second material has a first cavity over the variety of openings in the first material, in which the second material has a characteristic of being formed through a photolitrography process. The first material and the second material form an opening plate.
[031] In yet another general modality, a plate with opening adapted for use in the dispersion of liquids produced by a process that includes the steps of: a) the deposition of a layer of releasable seed on a substrate, b) the application of the first standardized photolithography mask over the releasable seed layer, the first standardized photolithography mask has a negative pattern for a desired opening pattern, c) the galvanization of a first material on the exposed portions of the releasable seed layer and limited by the first mask forming a substantially planar structure that has a variety of openings through it, d) the application of a second photolithography mask over the first material, the second photolithography mask has a negative pattern for a first cavity, in which the first cavity is positioned above the variety of openings, e) the plating of a second material on the exposed portions of the prim the material and limited by the second mask, f) removing both masks and g) stripping the releasable seed layer to release the first material and the second material.
[032] According to one or more modalities, a process for making plates with aperture with aperture size and shape precisely defined to satisfy a specific drop shape and drop size distribution is presented. In addition, the photodefined approach of the present invention allows flow rate decoupling from the drop size and / or size distribution. Therefore, the present invention allows the production of the opening plate in which the flow rate and drop size and / or size distribution can be approached and controlled independently of each other, which is another significant advantage over the technique. previous. In addition, the modalities described here provide scalability capable of manufacturing large volumes by removing laborious and costly steps in the manual process (for example, manual collection and drilling) from manufacturing processes. Prior art methods use a manual process called “collecting” to peel a final coated material from a support substrate (for example, the mandrel) and then drill through the plate material to a desired diameter to be used as opening plates .
[033] According to one or more modalities, a method for the manufacture of an opening plate, mesh, perforated plate, etc., for a liquid nebulizer, such as a vibrating mesh nebulizer comprises a photolitrography process, which ensures precise definition and control of aperture size. This photolithography method of making opening plates can, in one or more modalities, provide a plate with parametrically controlled opening to meet the desired specifications for dispensing a wide variety of liquid dispensing applications, such as dispensing drug formulations. in aerosols. In addition, the photo-defined process has significant potential to significantly improve process performance and thus offers significant potential for reducing manufacturing costs.
[034] According to some modalities, the semiconductor process techniques can be applied to the manufacturing method of the present invention to allow a completely automated process flow for the manufacture of opening plates through the creation of a photomask. In addition, instead of being limited to stainless steel substrates, a more conventional silicon wafer can be used together with a convenient release process using a release layer and a pickling process to remove the release layer, such as a wet release pickling process.
[035] Now in relation to figures 3A-3B, a cross-sectional view and a top view of a plate with aperture 300 formed through a photolitrography process are demonstrated according to one embodiment. As can be seen in figure 3A, the opening plate 300 includes a variety of openings 302, a cavity 304 and the side walls 306. The opening plate 300 is used to disperse a liquid, according to preferred embodiments. Opening plate 300 comprises a first material 308 having a variety of openings 302. The first material 308 is a layer having a thickness Φ3, the same as the height of the openings 302. The first material 308 has one or more characteristics that result from formation through a photolitrography process, such as a smooth surface, well-controlled diameters (Φ1, Φ4) and level (Φ5), uniform dimensions, etc. The opening plate 300 also comprises a second material 310 (which may comprise the same material or a different material than the first material 308) which is positioned directly or indirectly above the first material 308, such that the first material 308 can form the openings 302 and the second material 310 can define the cavity 304 and forms the side walls 306. The cavity 304 limited by the second material 310 is positioned above a variety of openings 302 in the first material 308. The second material 310 is a layer having a thickness equal to the depth of cavity 304, for example, Φ2-Φ3. The second material 310 also has one or more characteristics resulting from the formation through a photolitrography process, as previously described.
[036] In one approach, each of the variety of openings 302 of the first material 308 can have a Φ4 diameter of between about 1 μm and about 5 μm. In another approach, a de3 thickness of the first material 308 close to the range of openings 302 can be between about 5 μm and about 10 μm.
[037] As shown in figure 3A, in one embodiment, a height Φ2 of side walls 306 can be between about 40 μm and about 80 μm, such as about 60 μm, 65 μm, etc. In another embodiment, a de1 width of cavity 304 can be between about 50 μm and 80 μm, such as about 60 μm, 65 μm, etc. In preferred embodiments, the height Φ2 of the side walls 306 can correspond to a width Φ1 of the cavity 304. In one or more embodiments, the level Φ5 (a measured distance between openings) of one or more of the openings 302 can be between about 2 μm to 20 μm, or about 4 μm to 10 μm or any value or within that range. In some embodiments, the level selection impacts or affects the flow rate and / or the mechanical strength of an opening plate. In some embodiments, the level selection is a function of mechanical considerations, such as the frequency of vibration.
[038] Now in relation to figure 3B, a view of the top of a plate with opening 300 is shown, according to one embodiment, taken from line 3B in figure 3A. Referring again to figure 3B, an opening pattern is shown to have a star shape, however any shape or configuration can be used as desired, such as circular, square, triangular or freeform, etc. The process of the present invention allows formation in an opening plate 300 a number of openings 302 significantly greater than that which could be formed in an opening plate according to the prior art. This is due to the process described here according to various modalities that allows more freedom and precision in defining opening patterns, opening density, opening shape and opening size as desired to achieve the desired liquid distribution results. In addition, modalities described here may make use of a larger percentage of an opening plate area, because the opening size is not dependent on the thickness of the opening plate. In other words, the thickness is decoupled from the opening size, in contrast to the opening plates produced by galvanizing the prior art, in which the thickness of an opening plate is interrelated with the size of the openings. Therefore, more openings 302 per unit of open plate area are possible with a potential benefit of increased productivity while maintaining control of particle size and / or particle size distribution. In some embodiments, the number of openings 302 can vary from about 1 opening to about 1000 openings per mm2. For a typical sized opening plate (ie 20 mm2) for delivery to the lung of a nebulized liquid medicine, the number of openings can vary from about 50 to about 25,000 or about 300 to about 10,000 or any range number or value between them. Figure 3B illustrates a configuration in which 10,000 or more openings can be formed. In a modality of a nebulizer device, which has about 20 mm2 of opening plate, there can be 500 to 5,000 openings, for example, 1,000 to 3,000 or any range or value between them. Although there is no practical lower limit on the number of openings (for example, one is the minimum) that can be formed on an open plate, the process of the present invention allows for an extremely increased number, such as 500 or 1,000 or more per mm2 .
[039] In one or more embodiments, the opening outlet port (also referred to as an outlet) can have a diameter in a range of about 0.5 μm to about 10 μm and, in some modalities, this can vary at about 1 μm to about 6 μm, about 1 μm to about 4 μm, about 1 μm to about 3 μm in diameter, etc., or any range or value between them. An opening size distribution can vary from any desired smaller size to any desired larger size, and there is no need for standard deviation between size of openings according to various modalities. The process described above, in one embodiment, advantageously allows better control over the opening size than the prior art processes, in addition to which opening plates can be produced repetitively and reliably with much smaller opening orifices, such as 0 , 5 μm, 0.4 μm, 0.3 μm, 0.2 μm, 0.1 μm, etc. Furthermore, according to the modalities presented here, the process is capable of better control precision in obtaining the desired opening size, and consequently, a more tightly controlled range, that is, a more pronounced distribution curve. It should be noted, however, that the modalities presented here also allow a plate with an opening in which the openings can be purposefully formed in order to have different sizes from each other, such as a set of 3 μm of openings and a set 1 μm of openings on the same opening plate.
[040] According to the modalities of the present invention, the diameter Φ4 of the openings 302, the height Φ2 of the side walls 306, the thickness Φ3 of the first material 308 close to the variety of openings 302, the width Φ1 of the cavity 304 and / or the Φ5 level can be controlled independently, such as to provide a desired flow rate, droplet size and droplet size distribution when dispersing a liquid through openings 302.
[041] According to some modalities, The first material 308 and / or the second material 310 may include any suitable material, such as at least one of Ni, Co, Pd, Pt, their alloy and mixtures of these, among others suitable materials. A suitable material can be any galvanizable material and, in some other embodiments, the material chosen may have a resistance to the chemical properties of a liquid to be dispersed with a plate with opening 300.
[042] Now in relation to figures 4A-4B, a cross-sectional view and a top view of a plate with aperture 400 formed through a photolitrography process are demonstrated according to one modality. As can be seen in figure 4A, a plate with opening 400 includes a variety of openings 402, the first cavity 404, the second cavity 408 and the side walls 406. A plate with opening 400 can be used to disperse a liquid, according to with the preferred modalities.
[043] The opening plate 400 includes a first material that has a variety of openings 402. The first material 410 is a layer that has the same thickness Φc as the height of the openings 402. The first material 410 has a characteristic of being formed through a photolitrography process, such as smooth surfaces, uniform growth, etc., as previously described. Opening plate 400 also includes a second material 412 (which may be the same material or a different material than the first material 410) which is positioned directly or indirectly above the first material 410, the second material 412 which has a first cavity 404 above of a variety of openings 402 in the first material 410. The second material 412 is a layer that has the same thickness as the depth Φe of the first cavity 404. The second material 412 also has a characteristic of being formed through a photolitrography process such as described earlier, which results in one or more beneficial properties of smooth surfaces, well-controlled diameters (Φa, Φd and Φf) and level (Φg), uniform dimensions, etc.
[044] The opening plate 400 also includes a third material 414 having a second cavity 408, the third material 414 being positioned above the second material 412 such that the cavities 404 and 408 are positioned one above the other. The third material 414 is a layer having the same thickness as the depth of the second cavity 408, for example, Φb - (Φc + Φe). The third material 414 has a characteristic of being formed through a photolitrography process as previously described, the second cavity 408 is above the first cavity 404 and the inner diameter Φa of the second cavity 408 is greater than the internal diameter Φf of the first cavity 404.
[045] In one approach, each of the variety of openings 402 of the first material 410 can have a diameter Φd between about 1 μm and about 5 μm. In another approach, the Φc thickness of the first material 410 near the aperture variety 402 can be between about 5 μm and about 10 μm, such as about 6 μm.
[046] As shown in figure 4A, in one embodiment, the height Φb of the side walls 406 can be between about 40 μm and about 80 μm, such as about 60 μm, 65 μm, etc. In another embodiment, the width Φf of the first cavity 404 can be between about 20 μm and 30 μm, such as about 25 μm. In another embodiment, the depth Φe of the first cavity 404 can be between about 20 μm and 30 μm, such as about 25 μm. In preferred embodiments, the height Φb of the side walls 406 may correspond to the width Φf of the first cavity 404 and / or second cavity.
[047] Now in relation to figure 4B, the top view of a plate with opening 400 is shown, according to one embodiment, taken from line 4B in figure 4A. Again with reference to figure 4B, an opening pattern is shown to have three openings 402, however any shape and any number of openings 402 can be produced, as desired. According to preferred embodiments, the diameter Φd of the openings 402, the height Φb of the side walls 406, the thickness Φc of the first material 410 next to a variety of openings 402, the width Φa of the second cavity 408, the width Φf of the first cavity 404 and the Φg level can be controlled independently of each other, such as to provide the desired flow rate and droplet size when dispersing a liquid through the openings 402.
[048] According to some embodiments, the first material 410, the second material 412 and / or the third material 414 can comprise any suitable material. In some embodiments, materials can be appropriately selected from the group of platinum metals. In some embodiments, the materials comprise at least one of Ni, Co, Pd, Pt, their alloy and mixtures of these, among other suitable materials. The 400 opening plate can be constructed of a high strength and / or corrosion resistant material. As an example, the plate body (for example, the first material 410, the second material 412 and / or the third material 414) can be constructed of palladium or an alloy of nickel and palladium. Palladium or a nickel-palladium alloy is corrosion resistant to many corrosive materials, especially solutions for treating respiratory diseases by inhalation therapy, such as albuterol sulfate or an ipratropium solution, which can be used in medical applications. In some embodiments, at least one of the first, second and / or third material has a low modulus of elasticity and can result in lower stress for a given range of oscillation. Other materials that can be used to build the plate body include stainless steel, stainless steel alloys, gold, gold alloys and the like. A suitable material can be any galvanizable material and, in some other modalities, the chosen material can be inert and / or have chemical resistance to a dispersed liquid to be used with a 400 opening plate.
[049] The openings of a plate with opening in any mode can have an exit orifice that has a diameter anywhere within the range, from about 0.5 μm to about 6 μm, to produce drops that are about 0.5 μm to about 6 μm in size. In other embodiments, the opening outlet hole (also referred to as an outlet) can have a diameter of about 1 μm to about 4 μm, about 1 μm to about 3 μm, etc., or any range or value between them, to produce drops in about a corresponding size. Generally, the size of the droplet is approximately equal to the size of the exit orifice, however droplets that do exit may form and become slightly larger or smaller, depending on characteristics, such as surface tension and / or rheological properties, of a liquid being scattered. Exit orifice is used here to signify the opening from which the drop emerges and which can also be considered as the downstream or distal for the liquid supplement. This is contrasted with the inlet port, also referred to as a liquid supply opening, which is the opening in contact with or close to the liquid supply to be dispersed. The liquid supply opening is even larger in diameter and / or area than the outlet port. In some embodiments, the liquid supply opening can vary in size from about 20 μm to about 200 μm in diameter including any range or value between them.
[050] In one or more embodiments, openings can be formed (as shown, for example, in figure 3B and / or 4B) to describe a series of concentric reducing cylinders within an opening plate (as seen from the hole) inlet to outlet port). In some embodiments, the openings can be formed to describe two concentric cylinders inside an opening plate, as shown in figure 3B. In such embodiments, the liquid inlet port can be from about 20 μm to about 100 μm in diameter, and the outlet port can be from about 0.5 μm to about 6 μm in diameter. In some embodiments, the diameter of the outlet orifice can be from about 1% to about 10% of the diameter of the inlet orifice. More especially, in one or more embodiments, an inlet port may comprise a diameter of about 50 μm to about 80 μm and an outlet port may comprise a diameter of about 1 μm to about 4 μm.
[051] In one or more modalities, the openings can be formed in a plate with opening as three concentric cylinders, as shown in figure 4B. According to one or more embodiments, three or more concentric cylinders can be used to form within an opening plate to describe the opening (s). In such embodiments, the openings comprise a cylindrical inlet hole, one or more intermediate cylindrical openings and one or more cylindrical outlet holes formed in an opening plate. These openings can have diameters ranging anywhere from about 50 μm to about 200 μm for the inlet, about 10 μm to about 40 μm for the intermediate opening and about 1 μm to about 5 μm for the exit hole. It should be noted that the concentric cylinder arrangement of openings does not necessarily imply that the openings are coaxial. In some embodiments, as illustrated, for example, in figures 3, a variety (two or more) of outlet holes may be formed within the diameter of the largest inlet hole. In addition, multiple openings 302 (the exit holes) are typically formed within the area circumscribed by opening 304 (the entry hole). These outlet holes can be formed in a variety of patterns, configurations and positions relative to a major aperture axis. Although a smooth opening is usually obtained, some angle in the side walls of the opening can occur due to the attenuation of light in the lithography process. This angle tends to be more pronounced as the opening size decreases. Generally, an angle of the side walls of a given opening does not negatively affect the drop ejection performance and can, in some embodiments, be beneficial.
[052] In some embodiments described here, the openings generally describe an inverted ziggurat shape on the opening plate. In particular, when we refer to the modality described by figures 4, the ziggurat format is remarkable. The ziggurat shape can be used to provide mechanical strength to the opening plate, such that the opening plate is capable of being used in a vibrating mesh type nebulizer and can withstand the forces exerted on the opening plate due to vibration. The shape of the opening plate (for example, ziggurat shape) is not necessarily used to provide a particular size or size distribution of the resulting drops.
[053] Conveniently, the opening plates described herein according to various modalities can be formed in a dome shape (although other configurations, such as planar and quasi-planar, are suitable) as generally described in U.S. Patent No. 5,758,637, previously incorporated by reference. Typically, the opening plate will be vibrated at a frequency in the range of about 45 kHz to about 200 kHz when dispersing a liquid. In addition, when dispersing a liquid, the liquid can be placed in contact with a rear surface of the opening plate where the liquid adheres to the rear surface by the force of the surface tension. Upon vibration of the opening plate, drops of liquid are ejected from the front surface as generally described in US Patent Nos. 5,164,740; 5,586,550 and 5,758,637, previously incorporated by reference.
[054] Now in relation to figure 6, a method 600 for the manufacture of an opening plate is demonstrated according to a modality. Method 600 can be performed in any desired environment and can include more or less operations than those shown in figure 6, according to various modalities.
[055] In operation 602, the releasable seed layer is deposited above a substrate. The releasable seed layer may preferably comprise a peelable material, such as a metal, for example, a conductive metal. In some embodiments, the metal is one or more of: Al, Cu, Si, Ni, Au, Ag, steel, Zn, Pd, Pt, etc., their alloy, such as bronze, stainless steel, etc., mixture of precedents and the like. In some embodiments, the releasable seed layer may comprise a pickable conductive material, such as conductive metals such as Au, Ti, Cu, Ag, etc., and the alloy thereof. Of course, any other material can be used for the releasable seed layer as would be understood by those skilled in the art after reading the present descriptions.
[056] In operation 604, a first standardized photolithography mask is applied above the release layer. The first patterned photolithography mask has a negative pattern for a desired aperture pattern.
[057] The aperture size can be precisely defined through patterns of the photolithography mask (points in photography (photo dots)) made through the photolitrography process. As compared to prior art methods that use a galvanizing process, the opening is formed through a three-dimensional growth of coating materials.
[058] In one approach, the first standardized photolithography mask can give openings to the first material having a diameter of between about 0.5 μm and about 6 μm.
[059] In operation 606, a first material is galvanized above exposed portions of the releasable seed layer and limited by the first mask. In one approach, the first material close to the openings can be formed to a thickness that is independent of a diameter of the openings, such as between about 5 μm and about 10 μm, according to some modalities.
[060] The height of the first standardized photolithography mask and the thickness of the first material close to the openings are factors in determining the performance of the opening plate after the formation is complete. Figure 5A shows a scanning electron microscope (SEM) image from a top-down view of an internal side of an opening from the opening plate produced by the methods described herein. As can be seen, the edges of this opening are smooth and the shape is substantially uniform. The opening shown in figure 5A was produced by coating the first material to a thickness that was less than a height of the first standardized photolithography mask, thereby ensuring that the material was deposited evenly.
[061] Now in relation to figure 5B, which is a SEM image of a top-down view of an internal side of a plate with an opening produced using the methods described here, some advantages of the methods are notable. The openings in this opening plate were produced in the same way as the opening in figure 5A. The opening plate shown in figure 5B has three planar surfaces, with each inner surface being recessed from the next closest outer surface, similar to an opening plate shown in figures 4A-4B. Again in relation to figure 5B, it can be seen that the openings are precisely controlled in positioning and size and an opening plate has substantially vertical and substantially smooth walls. This precise manufacturing capacity is an advantage for the methods described here, according to several modalities, when compared to conventional manufacturing methods, such as galvanizing.
[062] In some embodiments, the diameter of the openings and the level of the openings can be chosen (dependent or independently) such that the thickness of the first material close to the openings and a flow rate of the liquid dispersed through the openings is controlled to achieve a desired value or range.
[063] In another embodiment, the thickness of the first material close to the openings can be independent of a positioning density of the openings in the opening pattern.
[064] In operation 608, a second photolithography mask is applied above the first material. The second photolithography mask has a negative pattern for a first cavity.
[065] In operation 610, a second material is galvanized above exposed portions of the first material and limited by the second mask.
[066] In one approach, the first material and the second material can be the same material. In another approach, the first material and the second material may comprise a galvanizable material having resistance to a dispersed liquid.
[067] In operation 612, both masks are removed using any technique known in the art. In one embodiment, both masks are removed in a single step, for example, they are removed at the same time.
[068] In operation 614, the releasable seed layer is stripped to release the coated materials. A preferred pickling includes a wet pickling process, among other methods of removing the release layer.
[069] In one embodiment, method 600 may include more operations, such as those described below.
[070] In an optional operation, a third photolithography mask can be applied above the second material, the third photolithography mask has a negative pattern for a second cavity. This third photolithography mask can be applied before removing the first and second mask. Then, a third material can be galvanized above exposed portions of the second material and defined by the third mask. All masks can be removed after galvanizing is complete. The second cavity can be above the first cavity and an internal diameter of the second cavity can be larger than an internal diameter of the first cavity.
[071] According to some modalities, the first material, the second material and / or the third material can comprise any suitable material. In some embodiments, materials can be appropriately selected from the platinum group. In some embodiments, the materials comprise at least one of Ni, Co, Pd, Pt and their alloy, among other suitable materials. The first material, the second material and / or the third material can comprise a high strength and corrosion resistant material, in one embodiment. As an example, the first material, the second material and / or the third material can comprise a nickel and palladium alloy. Such an alloy is resistant to many corrosive materials, especially solutions for treating respiratory diseases by inhalation therapy, such as a solution of albuterol sulfate or ipratropium, which can be used in medical applications. In addition, the nickel and palladium alloy has a low modulus of elasticity and, therefore, less stress for a given range of oscillation. Other materials that can be used for the first material, the second material and / or the third material include palladium, nickel and palladium alloys, stainless steel, stainless steel alloys, gold, gold alloys, and the like.
[072] To increase the droplet production rate, keeping the droplets within a specific size range, the openings can be constructed to have a certain shape. In one or more embodiments, the openings can be formed to describe a ziggurat shape on an opening plate. Using this approach, the opening plates can be formed as a series of concentric stepped down cylinders (as seen from the side of the entrance to the exit hole). In some embodiments, the opening plates can be formed as two concentric cylinders. In such embodiments, the liquid inlet can be about 50 μm to about 100 μm and the outlet port can be about 0.5 μm to about 6 μm. More especially, in one embodiment, an inlet port may comprise a diameter of about 60 μm to about 80 μm and an outlet port may comprise a diameter of about 1 μm to about 4 μm.
[073] According to one or more modalities, the plates with opening can be formed as three or more concentric cylinders. In such embodiments, there is an inlet cylinder, one or more intermediate cylinders and an outlet plate having outlets formed therein. In some embodiments, the diameter of the outlet orifice for the outlets formed therein may be about 1% to about 50% of the inlet orifice diameter. In some embodiments, the smallest close opening diameter can be about 10% to about 30% of the largest close opening diameter. For example, diameters can range anywhere from about 50 μm to about 100 μm for the inlet, about 10 μm to about 30 μm for the intermediate and about 1 μm to about 5 μm for the outgoing ones. In any of the foregoing, the openings describe an inverted ziggurat shape on an opening plate. Such a format provides a robust opening plate and can provide flow rate benefits, such as increasing the flow rate, while maintaining the size of the drops. In this way, the opening plate can find particular use with inhalation drug delivery applications. It should also be noted that the opening walls are generally described as smooth, that is, the opening walls describe a section of a geometric shape of regular circular cylinder. In other words, the opening walls are typically perpendicular to the plane of the opening plate or at a tangent to the dome-shaped plate. In some embodiments, however, the opening walls may have some angle and / or may even assume a tapered cross section.
[074] According to one approach, the opening plate can be formed in a completely automated process, which does not require manual stamping procedures.
[075] Now in relation to figures 7A-7L, the method is described schematically.
[076] In figures 7A-7B, the releasable seed layer 704 is deposited above a substrate 702. In preferred embodiments, the substrate 702 can comprise Si and the releasable seed layer 704 can include any pickable conductive metal.
[077] In figures 7C-7E, a first patterned photolithography mask 710 is applied above the releasable seed layer 704. The first patterned photolithography mask 710 has a negative pattern for a desired aperture pattern and can be formed by photoresist of the rotation coating 706, applying a photomask 708 which has a desired pattern to expose portions removed from photoresist 706 and dissolving the exposed portions by any method known in the art, such as by using a developer known in the art, additionally creating the first 710 mask.
[078] In figure 7F, a first material 712 is galvanized above exposed portions of the releasable seed layer 704 and the patterns are defined by the first mask.
[079] In figures 7G-7I, a second photolithography mask 714 is applied above the first material 712. The second photolithography mask 714 has a negative pattern for a first cavity. The second photolithography mask 714 can be formed by photoresist of the rotating coating 716, applying a photomask 718 that has a desired pattern, exposing removed portions of photoresist 716 and dissolving the exposed portions by any method known in the art, such as by using a developer known in the art, additionally producing the second mask 714.
[080] In figure 7J, a second material 720 is galvanized above exposed portions of the first material 712 and the patterns are defined by the second mask. Then, the second mask 714 and the first mask 710 are removed by any technique known in the art, resulting in the structure as shown in figure 7K. Then, the releasable seed layer 704 is stripped to release both the first material 712 and the second material 714, resulting in a structure as shown in figure 7L. A preferred pickling includes a wet pickling process. Other pickling processes that may be suitable methods of removing the release layer include plasma pickling and photochemical pickling.
[081] In preferred embodiments, the first material and the second material can form an opening plate for use in dispersing liquids in a vibrating mesh nebulizer. In these modalities, the photodefined approach allows flow rate control regardless of the droplet size due to the opening size and the standard opening density can be independently controlled.
[082] For example, the flow rate of an aerosol liquid generator is expected to be proportional to the number of total openings (which when combined with the size of each opening results in the total opening area). This is another significant advantage over the prior art where the standard opening density is limited by the required coating thickness. As a result, the methods discovered here for making open plates can provide a plate with a parametrically controlled opening to meet the desired specifications for the delivery of a wide variety of liquid drug formulations.
[083] According to one embodiment, an opening plate produced using the methods described here can include openings of various sizes, various domains, various formats, various profiles, various geometries, etc. For example, an opening plate may comprise one or more domains comprising a variety of openings arranged in a circular pattern, together with one or more domains comprising a variety of openings arranged in a non-circular pattern, such as elliptical, triangular or quadrilateral. The openings in the different domains can have variant or identical areas, such as diameters ranging from about 1 μm to about 5 μm.
[084] The openings may further comprise the same dispersion in relation to the area of the opening plate, a different dispersion or may be dispersed equally and differently, as in different domains. In another embodiment, an opening plate can include openings that have a first domain in an inner portion and openings that have a second domain in an outer portion. In addition, the photolithographic process described here allows the production of the slab with its own opening in varying patterns or geometries. In addition, the opening plates can be readily formed to be circular, elliptical, quadrangular and / or star-shaped, for example. The guides or projections can be formed on the opening plate to assist in the manufacture of a nebulizer with the same, in some modalities. It is clear that any other arrangement of openings, size of openings, opening range, opening profiles, etc., can be produced using the methods described herein, as would be understood by those skilled in the art after reading the present descriptions.
[085] The methods discovered here do not require strict alignment tolerance between layers due to the displacement of the two or more layers to provide a good alignment margin. The additional advantages over the galvanizing process of making slabs with opening include the fact that the photo-defined opening size is not related to the coating thickness. Therefore, using a photo-defined process allows for improved process control and potential improved manufacturing performance. The dependence of the opening size on the coating thickness has been a significant factor in the loss of yield by conventional galvanizing processes, which can now be avoided using the techniques described here. Also, multilayer processes can be used to achieve a desired open end plate geometry, which was not possible using conventional open plate forming techniques.
[086] The open plates were constructed using the processes described here and the aerosol test data for these open plates appears below in Table 1 for performance comparison. Table 1 shows the results of the tests of three plates with photodefined opening according to the modalities described here and three plates with galvanized opening according to the prior art.

[087] In Table 1, the TCAG indicates which sample of an aerosol generator with a tubular core was tested, the VMD indicates the median volume diameter that is determined based on the size of the drops coming out of the opening plate, the GSD indicates a distribution geometric pattern and is the calculation of (D84 / D50) and the Space indicates the space of the calculation of (D90-D10) / D50, where D is the drop size in the percentile (as indicated by the subscribed numbering) of the size distribution of the drop that was measured by light scattering technology, such as a Malvern light scattering instrument. For example, for a P35 photodefined unit, the light scattering method measures Dio = 1.414 μm, D50 = 2.607 μm, D84 = 4.038 μm, D90 = 4.844 μm, then GSD = D84 / D50 = 1.549. For a F007 galvanized unit, the light scattering method measures Di0 = i, 585 μm, D50 = 4.245 μm, D84 = 8.052 μm, D90 = 8.935 μm, then GSD = D84 / D50 = i, 897.
[088] As a comparison, the drop size distribution for photo-defined units is 79% more limited than for galvanized ones when assuming the same D50 value, which indicates better controlled drop size of aerosol medicine and dosage more effective distribution to the lung.
[089] As can be seen in Table i, plates with aperture produced using the methods described here (P35, P42, P43) have a lower GSD than plates with aperture (F007, F038, F044) produced conventionally (prior art) ). A smaller droplet size (close to i-2 μm) is considered very desirable to achieve distribution in the deep lung. A smaller GSD corresponds to a more limited drop size distribution produced by the opening plate, which is a desirable feature for effective targeted delivery to the lung.
[090] The units tested and tabulated in Table 1 are “hybrid” opening plates. Here, the term “hybrid” means that the openings and the geometry of the opening plate are defined through the photolithographic process, however the opening plates are made on stainless steel substrates and harvested from the substrate instead of Si or some other material. substrate. The first prototype made using the methods described here shows promising results. It distributes at a flow rate of up to 1.2 mL / min with average sized drops of 3.3 μm. For comparison, a typical galvanized plate device with distribution opening at a flow rate of only 0.3 mL / min with an average drop size greater than 4.6 μm. The photodefined opening plate is also capable of delivering an even smaller droplet size, about 2.7 μm at a flow rate of 0.4 mL / min. This is a significant improvement over an opening plate manufactured using the prior art galvanizing process. Significant improvement is achieved in the size distribution of the smaller droplets in the VMD and in obtaining a more limited size distribution, for example, the GSD and the Space for plates with photo-defined openings against those galvanized. Another improvement in opening size, opening shape and / or size distribution control is expected with completely photodefined processes, in which stainless steel substrates are replaced with high quality Si substrates. In addition, a more precisely controlled aperture size can be achieved from the photolithographic process of the present invention which is demonstrated in the results of Table 1.
[091] Slotted plates can be constructed so that the volume of liquid in a range of about 4 μL to about 30 μL can be dispersed within a time span of less than about one second by using a plate with an opening that has about 1000 openings, according to some modalities. In addition, the droplet size and droplet size distribution resulting from dispersion across the opening plate of the present invention can result in a respirable fraction (for example, that fraction of drops that reaches the deep lung), that is, greater that about 40% or 50% or 60%, 70% or 80% or 90% or 95% or 98% or 99% in many. In one or more modalities, this breathable fraction is achieved by using the opening plate of the present invention with a piezo-driven nebulizer, with a vibrating mesh, such as those described in US Patent Nos. 5,164,740. 5,586,550 and 5,758,637, previously incorporated by reference. In this way, a drug can be dispersed and then efficiently inhaled by a patient.
[092] Now in relation to figures 8A-8B, a vibrating mesh type nebulizer is demonstrated according to one modality. As shown in figure 8A, an opening plate 800 can be configured to have a curvature, as in a dome shape, which can be spherical, parabolic or any other curvature. Of course, in other embodiments, the opening plate 800 can be substantially planar and is not limited to the arrangement shown in figures 8A-8B. The opening plate 800 can be formed to have a dome portion 808 over its majority and this can be concentric with the center of the opening plate 800, still leaving a portion of the plate opening 800, that is, a peripheral ring portion substantially planar 812. The opening plate 800 can have a first face 804 and a second face 806. As shown in figure 8B, the plate with opening 800 can also have a variety of openings 814 therethrough. The first face 804 can comprise a concave side of the dome portion 808 and the second face 806 can comprise a convex side of the dome portion 808 of the opening plate 800. The openings 814 can be conical to have a wide portion at the entrance 810 in the first face 804 and a limited portion at outlet 816 on the second face 806 of the opening plate 800 or it can be substantially straight from inlet 810 to outlet 816.
[093] Typically, a liquid is placed on the first face 804 (also referred to as the liquid supply side) of the opening plate 800, where it can be dragged into the entrance 810 of the openings 814 and emitted as a fog or scattered cloud. 822 from the outlet 816 of the openings 814 on the second face 806 of the opening plate 800.
[094] The plate with opening 800 can be mounted on an aerosol valve 802, which defines an opening 810 through it. This can be done in such a way that the dome portion 808 of the opening plate 800 protrudes from the opening 810 of the aerosol valve 802 and the substantially planar peripheral ring portion 812 on the second face 806 of the opening plate 800 touches the first face 820 of the aerosol valve 802. In another embodiment where the opening plate 800 is substantially planar, the portion of the opening plate 800 where the openings 814 are positioned can be placed in opening 810 of the aerosol valve 802. A vibrating element 840 can be supplied and can be mounted on the first face 820 of the aerosol valve 802 or alternatively it can be mounted on a second opposite face 830 of the aerosol valve 802. The opening plate 800 can be vibrated in such a way as to suck up the liquid through the openings 814 of the opening plate 800 from the first face 804 to the second face 806, where the liquid is expelled from the openings 814 as a mist.
[095] In some approaches, the plate with opening 800 can be vibrated by a vibrating element 840, which can be a piezoelectric element in preferred embodiments. The vibrating element 840 can be mounted on the aerosol valve 802, in such a way that the vibration of the vibrating element 840 can be mechanically transferred through the aerosol valve 802 to the opening plate 800. The vibrating element 840 can be annular and can circulate opening 810 of the aerosol valve 802, for example, in a coaxial arrangement.
[096] In some embodiments, an 860 circuit can supply power from a power source. The circuit 860 may include a switch that can be operable to vibrate the vibrating element 840, and thus the opening plate 800 and the dispersion carried out in this way can be achieved within milliseconds of operation of the switch. Circuit 860 may include a controller 870, for example, a microprocessor, programmable field gate matrix (FPGA), application specific integrated circuit (ASIC), etc., which can supply power to the vibrating element 840 to produce the liquid dispersed from the plate with aperture 800 within milliseconds or fractions of milliseconds of a signal to do so.
[097] In some cases, the opening plates described here can be used in non-vibrating applications. For example, opening plates can be used as a non-vibrating nozzle where liquid is forced through the openings. As an example, open plates can be used with inkjet printers that use thermal or piezoelectric energy to force liquid through the nozzles. The opening plates described here according to various modalities can be advantageous when used as non-vibrating nozzles with inkjet printers due to their corrosion resistant construction and potentially thinner opening size. Opening plates of the present invention may be suitable for other fluid distribution applications, such as medical applications for non-medicated delivery, fuel injection, precise liquid deposition and other applications where dispersion is useful, and especially where a benefit is realized by combining high yield and small, precise drop (particle) size. In many applications, the method of making openings, as described here according to various modalities, can pay for the costs and / or efficiency benefits even if precise drop size control is not an important aspect of the produced opening plate.
[098] Although several modalities have been described above, it should be understood that they were presented for the purpose of example only and without limitation. In addition, the scope and scope of a preferred modality should not be limited by any of the exemplary modalities described above, but should be defined only in accordance with the following claims and their equivalents.

权利要求:
Claims (17)
[0001]
1. Plate with nebulizer opening for use in the dispersion of a liquid in a nebulizer characterized by comprising: a first material (308) having a variety of first openings (302), the first material having a characteristic of being formed through a photolithography process and in which the variety of first openings define generally cylindrical shapes, the outlet opening of the first openings (302) having a diameter between 0.5μm and 6μm to produce droplets with the size between 0.5μm and 6μm; a second material (310) on the first material (308), the second material having a variety of second openings (304) on the variety of first openings (302) in the first material, the second material having a characteristic of being formed through a photolithography process and in which the variety of second openings (304) define generally cylindrical shapes defining liquid supply cavities, each liquid supply cavity having a diameter between 20μm and 200μm; wherein the first material (308) and the second material (310) form a plate with an opening for use in a nebulizer, and where a variety of first openings are within the diameter of a larger liquid supply cavity defined by a second opening .
[0002]
2. Opening plate, according to claim 1, characterized by the fact that the exit holes of the first openings have a diameter within a range of 1 μm to 4 μm.
[0003]
3. Opening plate according to claim 2 or 2, characterized by the fact that the exit holes of the first openings (302) have a diameter within the range of 1 μm to 3μm.
[0004]
4. Opening plate according to any one of claims 1 to 3, characterized by the fact that each liquid supply cavity has a diameter within a range of 20μm to 100 μm.
[0005]
Open plate according to any one of claims 2 to 4, characterized by the fact that the liquid supply cavities of the second openings (304) have a diameter within a range of 50μm to 80 μm.
[0006]
6. Opening plate according to any one of claims 1 to 5, characterized by the fact that the variety of first (302) and second (304) openings describes a ziggurat shape on the opening plate.
[0007]
Open plate according to any one of claims 1 to 6, characterized by the fact that it comprises three or more concentric cylinders, in which each variety of first (302) and second (304) openings generally describes straight sections of circular cylinder on the opening plate.
[0008]
8. Opening plate according to any one of claims 1 to 7, characterized by the fact that it has a geometric dome shape.
[0009]
9. Nebulizer type vibrating mesh characterized by the fact that it comprises an opening plate as defined in claim 8 and a vibrating element provides vibrational energy to the opening plate.
[0010]
10. Method for the manufacture of a plate with a nebulizing opening, the method characterized by the fact that it comprises: the deposition of a layer of releasable seed (704) on a substrate; applying a first standardized photolithography mask over the releasable seed layer (704), the first standardized photolithography mask (706) having a negative pattern for a desired first circular opening pattern; galvanizing a first material (712) above the exposed portions of the releasable seed layer (704) and defined by the first mask (706); applying a second photolithography mask (716) to the first material, the second photolithography mask having a negative pattern for the first circular cavity; galvanizing a second material (720) on the exposed portions of the first material (712) and defined by the second mask (716); removing both masks (706, 716); and stripping the releasable seed layer (704) to release the first material (712) and the second material (720), wherein the first material (712) and the second material (720) form an opening plate for use in dispersion of a liquid one in which the variety of first openings are within the diameter of a circular cavity.
[0011]
11. Method, according to claim 10, characterized by the fact that the first standardized photolithography mask (706) gives openings to the first material that has a diameter between 1 μm and 5 μm.
[0012]
12. Method according to claim 10 or 11, characterized in that the first material (712) near the openings is formed with a thickness that is independent of a diameter of the openings.
[0013]
Method according to claim 10 or 11, characterized in that it further comprises: applying a third photolithography mask on the second material (720), the third photolithography mask having a negative pattern with respect to the second circular cavity; galvanizing a third material over an exposed area defined by the third mask; and removing all three masks, where the second cavity is over the first cavity, and where an internal diameter of the second cavity is greater than an internal diameter of the first cavity.
[0014]
14. Method according to claim 13, characterized in that the first material (712), the second material (720) and the third material are the same material.
[0015]
15. Method, according to claim 10, characterized by the fact that the opening plate is formed in an automated process.
[0016]
16. Method according to claim 11 or 12, characterized in that the first material (712) and the second material (720) are the same material.
[0017]
17. Method according to claim 10, characterized in that the first material (712) and the second material (720) comprise a galvanizable material that has a resistance to the dispersed liquid.

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公开号 | 公开日

WO2012092163A1|2012-07-05|

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EP3795361A1|2021-03-24|

US20160130715A1|2016-05-12|

US10508353B2|2019-12-17|

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CN103415398A|2013-11-27|

HK1190367A1|2014-07-04|

BR112013016671A2|2016-10-04|

EP3437872A1|2019-02-06|

RU2593254C2|2016-08-10|

JP6235905B2|2017-11-22|

US20170350030A1|2017-12-07|

EP2658719B1|2018-08-29|

US10662543B2|2020-05-26|

RU2013129238A|2015-02-10|

CN103415398B|2016-08-10|

EP2658719A1|2013-11-06|

US20200347507A1|2020-11-05|

US20130334339A1|2013-12-19|

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法律状态:
2018-12-18| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

2019-07-02| B06T| Formal requirements before examination [chapter 6.20 patent gazette]|

2020-07-07| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|

2020-10-06| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

2020-12-15| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 23/12/2011, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

申请号 | 申请日 | 专利标题

US201061427715P| true| 2010-12-28|2010-12-28|

US61/427,715|2010-12-28|

PCT/US2011/067106|WO2012092163A1|2010-12-28|2011-12-23|Photodefined aperture plate and method for producing the same|

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