Microstructured filter

MICROSTRUCTURED FILTER FOR LIQUIDS AND SPRAY FILTER FOR INHALATION THERAPY

The present invention relates to a microstructured filter for liquids and a nebulizer containing said filter for inhalation therapy.

Filters having pores smaller than micrometre diameter are known, with pore size distribution statistically dependent on the material used. The outer dimensions of such a filter element are tens of times larger than the pore diameter, and tests have shown that they cannot be made as small as desired.

Also known are micro-apertured metal strips of up to 100 µm thickness for use in stencil printing machines, such as nickel, with apertures of a few micrometres in diameter evenly distributed throughout the strip. These strips are, for example, galvanically manufactured. However, such metal strips cannot be combined with microstructured components.

European Patent Specification EP-0321432 discloses a cross-flow microfilter to which a liquid to be filtered is introduced, to obtain a concentrate and a filtrate. Between the fluid inlet chamber and the filtrate collection chamber there are rows of bridges or ridges, which in turn are connected. The rows of bridges and junctions form a microfilter. The direction of the connection paths is inclined at 90 to 135 ° with respect to the direction of flow of the liquid / concentrate. The liquid that enters the concentrate flows through the rows of the protrusions. The filtrate is collected in the chambers and exits the filter either perpendicular to the filter surface or into the filter passageways between the passageways for the concentrate.

International Patent Application Publication WO93 / 11862 discloses a micromechanical filter consisting of three layers. The interlayer is located within the predetermined regions of the sealed base layer and is provided with a topcoat with openings. The openings are

EE 04773 B1 regions of elongated shape. There is no interlayer parallel to one or both sides of the openings. In these regions, the coating is formed in a cantilevered or protruding configuration. Below the openings under the cantilevered cavity, there is a shallow slot as wide as the interlayer and as long as the elongated opening. The filtrate flows through this slot into the filtrate collection chamber, which is wider than the intermediate chamber. The coating comprises a plurality of elongated openings arranged in parallel rows. The rows of slots are arranged on the cover in a meander shape. The liquid flows perpendicular to the filter surface through a set of openings into the inlet chambers and exits the filtrate collection chambers through openings perpendicular to the filter surface. The layers of this filter can be made of silicone, plastic or metal, and the filter is formed by etching, trimming, or machining, as thin-layer technology and metal vapor deposition can be applied.

These and other offered devices have a number of problems. For example, it is noted that at least some of the devices provided above are susceptible to blockages, which may cause the filter to stop working. To solve this problem, a larger filter is recommended, but such larger filters have an undesirably large unused volume. Thus, known filters are undesirably complicated and thus time consuming and expensive to manufacture. In addition, quite a number of known devices have the property of being incompatible with other microstructured components.

Accordingly, it is an object of the present invention to provide a microstructured filter for liquids that addresses one or more of the problems described herein.

According to one aspect of the invention, the invention relates to a microstructured filter for liquids having an inlet for an unfiltered liquid and an outlet for the filtered liquid, comprising:

a filter chamber free from inlet and outlet, said chamber being partially defined by a substantially flat base plate and a protective cover plate,

EE 04773 B1 a filter element in the filter chamber comprising protrusions each of which is common to and protruding from the base plate, the protrusions being separated from each other by connecting pathways forming a fluid flow path through the filter chamber from the inlet to the outlet; two adjacent rows and zigzagging through the filter chamber, and the inlet and outlet both have extended slots for unfiltered and filtered liquid, respectively, each slot being substantially as wide as the io filter chamber and substantially as high as the projections on the inlet and outlet sides of the filter element.

According to a preferred embodiment of the invention, the invention relates to a microstructured filter for liquids having an inlet for an unfiltered liquid and an outlet for the filtered liquid, wherein the flow of liquid through the entire filter occurs on the surface of the filter;

protrusions located in mutually opposing rows, preferably protruding from the flat base plate and being integral parts of the base plate, connections between the protrusions, and preferably a flat cover plate located above the protrusions, the connecting paths being passages from the inlet region to the outlet and the area between the rows of edges of the cover plate being approximately as large as the width of the connecting paths between these edges, extending a fluid stream passing through communication lines, an elongated inlet slot for the unfiltered fluid in the filter inlet extending approximately the entire width of the filter and approximately as high as the protrusions protruding from the base plate, and an extended outlet slit for the filtered fluid in the outlet approximately as high as the protrusions protruding from the base plate.

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Preferably, the height to width ratio of the input slit and the output slit is from 1: 5 to 1: 1000. Preferably, the inlet slit must adhere to coarser particles.

The rows of projections are staggered. The protrusions closer to the filter inlet portion are wider than the protrusions closer to the filter outlet portion.

The distance between the flat base plate and the flat cover plate in the region surrounding each row of protrusions, with the rows spaced, is preferably about as wide as the width of the communication paths on the side of the protrusions where the liquid passes through the lines of communication connections. The distance is preferably between half and two widths of the connection path. Preferably, the distance is reduced line by line when viewed downstream. Therefore, the cross-sections of the connections on the inlet side of the liquid may be approximately square.

The distance between the flat base plate and the flat cover plate in one row of protrusions may be constant. In the case of rows of projections arranged in a meander or zigzag pattern, this distance may be wider at the end of the row near the outlet of the filter than at the end of the row near the inlet. The distance preferably increases linearly from one end of the line of projections to the other end.

Opposite sides of two adjacent rows of protrusions may form a chamber into which fluid flows from all junctions between the first row of protrusions and out of which fluid flows into all junctions between adjacent rows of protrusions. Upstream of the first row of projections is an upstream collection chamber of extended cross-section, into which unfiltered liquid flows and outflows liquid into all connections between the first row of projections. Downstream of the last row of projections is a downstream collection chamber with an elongated cross-section, into which fluid flows from the junctions between the projections of the last row and from which the filtered liquid flows out.

The protrusions may be lattice or faceted, and as seen in the flow direction, either straight or curved. The protrusions may also have any cross-section preferably in the form of columns of straight EE 04773 B1 te. The cross-section is preferably round or polygonal.

Preferably, the length of the passageways between the bridges or the ridges is at least twice the height of the fluid inlet. Preferably, the cross-sections of the connecting paths are approximately rectangular or cylindrical or trapezoidal. In the latter case, the cover plate forms the long side of the trapezoid. Connections are, for example, 5 to 50 µm long, 2.5 µm high and 2.5 to 25 µm wide.

The distance between the rows of projections is preferably twice as large as the width of the connection path at the entry point. The rows of projections run parallel to each other, meander or zigzag. Zigzag lines are inclined at an angle of 2 to 25 ° relative to each other.

When the filter projections are arranged in a meander or zigzag pattern, the particles to be filtered are held in the region of the fluid inlet adjacent to the filter outlet, with the distance between the projections of the inlet portion progressively increasing from the region of the filter outlet. The filter is only completely clogged and exhausted if the inlet chamber between each of the two projections is almost completely filled with particles that need to be filtered out.

The filter separating capacity is preferably relatively well defined with a minimum of fluctuations in connection dimensions. The filter need not necessarily have a flow-rate regulator for the fluid to be filtered and a filter-fluid filtrate collector.

The filter can be made using known methods, for example, metal, silicone, glass, ceramic or plastic. The base plate may be made of the same material as the cover plate or of a different material. The filter is preferably usable under high pressure conditions, for example up to 30 MPa (300 bar).

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In a microstructured filter, according to another embodiment of the invention, microstructured fluid elements, such as an aerosol atomizer for spraying a liquid or aerosol under pressure, are arranged on the same base plate.

A microstructured filter according to various embodiments of the invention may have some or all of the following advantages:

since the filter has many connections on a small surface, the filter will work even if some of the connections are blocked by impurities in the liquid. This allows the filter to be used when the filter is disposed in a nozzle for administering a medicament to improve the performance of the nozzle, since dropping such a nozzle may lead to fatal consequences for the user;

the connections can be defined within narrow limits by shape, cross-sectional area and length (most preferred device has the same dimensions for each connection);

the cross-section of the junction may be adapted to other conditions and may be, for example, a cross-section of the nozzle, which in turn is connected downstream, the wide surface of the filter may be correlated with in the direction of flow, the open surface of the filter (sum of the cross-sectional areas of all communication paths) may be at least 50% of the total surface area of ​​the filter;

The microstructured filters described herein find use in the filtration of drugs dissolved in a particular solvent, which are used as an aerosol for inhalation.

Suitable solvents are, for example, water or ethanol or mixtures thereof. Suitable medications are

For example, Berotec, Atrovent, Berodual, Salbutamol, Combivent, Oxivent, Ba 679, BEA 2108 et al.

The filter of the present invention may also be used in the nozzle described in PCT application WO91 / 14468 or PCT / EP96 / 04351.

The microstructured filter described herein may be constructed as follows: a plurality of, for example, size plates connected to each other simultaneously microstructured over a wide surface and connected to a wide flat cover plate in a single operation (batch process). The composite assembly may be divided into a number of discrete parts.

This preparation has certain advantages. On the one hand, the batch production process allows the production of extremely inexpensive high precision individual particles having a structural accuracy of a few micrometres to submicrometric values, which can only be produced in series production at significantly higher costs. On the other hand, a batch production process allows for the uniform quality of all elements and the ability to reproduce all elements under the same conditions of the process, which is unlikely to change the element parameters slowly, which can occur in serial production due to equipment wear.

In addition, the positioning and positioning of parts during design is also predetermined by design, and is not done with expensive sorters such as the aforementioned assemblies.

The base plate can be made, for example, by reactive etching, galvanizing or, for plastics, by lithography, galvanization and molding according to the LIGM process. Next, a structuring process can take place to produce a profile of specific paths. Trapezoidal or cylindrical cross-sections may be made by special over or under etching techniques. Both types of construction can be made by dry etching as well as by etching

EE 04773 BI with wet etching. Triangular cross-section connections can be fabricated with monocrystalline and silicone based anisotropic operative etching of the base plate. The base plate is preferably structured with isotropic or anisotropic wet or dry etching or a combination thereof, particularly preferably with anisotropic dry etching.

The microstructured baseplate and its projections may be connected by anodic welding of a flat-faced silicone and a glass, such as an alkali borosilicate glass. In one example, a glass plate is placed on a microstructured io silicone plate and connected by electrode welding. The entire assembly is heated to 200 to 500 ° C and an approximate negative voltage of 1000 V applied between the silicone plate and the glass plate. Thanks to the applied voltage, positively charged alkali ions penetrate the glass at the cathode where they are neutralized. There is a negative spatial charge in the transition area between the glass and the silicone formed in the glass, which is applied to achieve electrostatic attraction of the two surfaces and which, in addition to oxygen bridge bonds, forms a permanent chemical bond between the glass surface and the silicone surface.

In the illustrative process described above, the use of a glass cover plate is particularly useful for achieving quench resistance, on the one hand, due to the quality of the ionic bonds, and, on the other, because defects or particles retained in the filter are easily identified by optical observation.

After the pairing operations, the resulting node can be divided into individual filters, preferably by a high speed rotating diamond saw blade, so that each filter inlet and outlet are visible unless previously visible. The incision may be made to within a few micrometres.

In addition to the use of anode bandages, the microstructured substrate may be joined to the cover plate by ultrasonic welding, laser welding, bonding,

EE 04773 B1 to one of ordinary skill in the art.

The devices according to the invention will now be described by way of example, with reference to the accompanying drawings.

In FIG. 1 is a schematic representation of a filter.

In FIG. 2 is an enlarged view of FIG. 1 shows the projection lines of the filter.

In FIG. Fig. 3 is a view of the embodiment of FIG. 2 cross-section along line AA.

In FIG. 4 is a schematic representation of the profiles of various protrusions.

In FIG. 5 is a schematic representation of other types of projections.

In FIG. 6 is a schematic representation of the arrangement of the projections.

In FIG. 7 shows an illustrative example of the orientation of the protrusions.

In FIG. 8 is an electron microscope image of a filter at the end of its life.

As noted above, FIG. 1 top view of an open filter that is later covered with a cover plate (not shown). The filter base plate 1 is microstructured in the region between the side regions 2a and 2b. Microstructures have resulted in rows 3 having a zigzag arrangement of projections. It can also be seen that rows 3 are inclined at an angle α to each other.

In this example, the base plate, in addition to the filter, is provided with a series of upstream projections which form a coarse filter to mix the fluid flowing therethrough.

Away from the protrusions 4 towards the inlet of the fluid flow is an inlet slot 5 through which

EE 04773 BIO enters an unfiltered liquid into the filter. The filter has an adjacent outlet 6 for discharging the filtered liquid. In this illustrative example, the outlet 6 forms a part with the base plate 1. It should be noted that the filter may be formed without the outlet 6 and the coarse filter 4.

In FIG. 2 is an enlarged view of the embodiment of FIG. 1, showing the arrangement of the protrusions in rows 3. The protrusions 7 are rectangular bridges or facets, and as described below, they may have an alternative configuration. It will be seen that the rows 3 include protrusions 7 that extend upwardly from the plane of the base plate 1 and are spaced apart to form a high quality liquid filter.

In FIG. 3 is a cross-sectional view of one row taken along line AA in FIG. 1. In this image, the projections 7 have concave long sides between which are interconnecting paths 8 of cylindrical ribs.

In FIG. Fig. 4 shows the possible profiles of the protrusions viewed from the original open side (i.e., top) of the filter. Any one of them, as well as a combination of them (or a protrusion of another shape) is suitable for use in the filter described herein.

FIG. 4 shows a rectangular portion 11, a portion 12 of elongated, constant width and rounded shorter sides, a portion 13 of a wingspan, a portion 14 and a portion 15 of constant width and one inclined shorter side, which is shaped like a disk segment. Also shown is a square column 16, a triangular column 17, a round column 18, and a polygonal column 19. As noted above, each of these projections is useful in a filter.

In FIG. 5 is a cross-sectional view of the various protrusions, in particular a rectangular cross-section of a protrusion 21, a protrusion 22 having a concave longitudinal section, a protrusion 23 of a trapezoidal cross section, the long side of a trapezoid being connected to a base plate 1, a trapezoidal

The shorter side of EE 04773 B1 is connected to the base plate 1 and to the projection 25 by two rounded corners.

FIG. 6 shows different variations of the arrangement of the projections, which are indicated by points of different sizes independently of the shape of the projections. The protrusions may be arranged as a matrix 31 or linearly in a row 32 or meandered 33 or zigzag 34. A set of protrusions arranged as rows 35 or meandered or zigzag 36 may be in the form of staggered cascades.

In FIG. 7 shows the orientation of the solids relative to the incoming fluid flow 41. As can be seen, some protrusions 42 are disposed parallel to the incoming fluid flow, while others 43 are disposed at different angles to the inlet flow. FIG. 7 is to be understood that the faces do not necessarily have to be oriented in the same way with respect to the input current. In fact, differently oriented facets are a distinguishing feature of the invention, which causes an improvement in the degree of fluid mixing as the fluid flows through the filter.

FIG. Fig. 8 shows a microstructured micrograph of a scanning electron microscope. 1 at the end of its useful life. The image is obtained through a glass cover plate (not shown). The image illustrates the filter with zigzagged rows of projections, although the projections are not visible at the selected magnification level.

The liquid flows through the filter in the direction of the arrow and the particles suspended in the liquid are trapped by adjacent protrusions. The rows of projections are covered with filtered particles, which are more near the side regions 2a and 2b than in the central part of the filter, where there are almost no particles between the projection rows which are in the liquid flow to the filter. Thus, the filter is fully operational in its area (i.e., liquid may still pass through the filter). As shown in FIG. 8th see, the outline between the free region of the filter and the clogged region is parabolic.

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Therefore, it can be seen that the filter described herein is less blocked than known filters, since it can function adequately even when a relatively large portion of the filter surface is clogged. The result of this designation is that the useful life of the filter and thus the life of the devices containing the filter can be considerably extended. This is in direct contrast to previously known devices, where the relatively low clogging of the filter causes the device to stop functioning accurately.

Example: Microstructured filter for sprayer

As noted above, the filter described herein is widely used in nozzles, and more particularly in nozzles for aerosolizing a drug-containing liquid.

An example of such a nozzle is described below. The filter is formed on the base plate with other microstructured components. The base plate is 2.6 mm wide and approximately 5 mm long. At a width of 2 mm, the plate contains 40 rows of projections arranged in a zigzag pattern. Each line is 1.3 mm long. The protrusions are rectangular facets 10 µm long by 2.5 µm wide and projecting from the base plate to 5 µm high. There are communication paths between the peaks, which are 5 pm high and 3 pm wide.

The inlet side of the filter fluid has a series of 10 rectangular facets 200 µm long and 50 µm wide, projecting from the base plate to 100 µm high. Between these facets there are communication paths which are 100 µm high and 150 µm wide. Ten risk-rectangular facets form a coarse filter and means for mixing the fluid stream passing through it. At a distance of 300 µm from the line of solids, there is a fluid inlet slot approximately 2 mm wide and 100 µm high. The filtrate collection chamber is zigzagged behind the rows. The filtrate collection chamber is 5 µm high and tapers gradually from a width of 2 mm and is connected to a rectangular outlet having a height of 5 µm and a width of 8 µm. In this example, the outlet is made simultaneously with microstructure of the base plate.

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The base plate, 1.5 mm thick, contains nickel and is manufactured from plastic casting by electroplating with 1083 full-grain structures. All of this is covered with a 0.8 mm thick nickel plate, which is secured to the base plate by soldering.