Microfluidic device and method of production

Abstract

The invention provides a microfluidic device (1), in particular a nozzle for an inhalation device, comprising at least two microfluidic structures (2A, 2A '), each of said structures (2A, 2A') being located at a front end (1B) of the microfluidic device; characterized in that the microfluidic device (1) is at least partially made of a single crystal material, and wherein the front end (1B) of the microfluidic device (1) and the microfluidic structures (2A, 2A ') are aligned with a crystal orientation line, as well as a method for producing the device and the use thereof.

Description

Technical Field

[0001] The present invention belongs to the field of microfluidic devices, methods of producing microfluidic devices and uses of said devices. In particular, the present invention relates to the production of microfluidic devices with high precision, in particular microfluidic devices for inhalation devices such as microfluidic nozzles. Background Art

[0002] Microfluidic devices are key components of many medical and scientific devices. For example, nebulizers and other aerosol generators utilize multiple microfluidic devices, particularly nozzles, valves, and pump systems.

[0003] Nebulizers or other aerosol generators for liquids have long been known from the art. Such devices are used in medicine and therapy, among other things. There, they are used as inhalation devices for applying active ingredients in the form of aerosols (i.e. droplets embedded in a gas). Such inhalation devices are known, for example, from document EP 0 627 230 B1. The main components of this inhalation device are: a reservoir, in which the liquid to be aerosolized is contained; a pumping unit, which is used to generate a sufficiently high pressure for atomization; and a spray device in the form of a nozzle.

[0004] In many inhalation devices, the nozzle is a microfluidic nozzle. In order to achieve a sufficiently uniform and fine mist of droplets, a relatively high pressure (such as 10 bar, up to 1000 bar) is usually required. In order to keep the amount of vaporized liquid in each dose acceptably low, the atomizing nozzle usually includes one or several channels, each channel having a diameter of only a few μm. 2 Order of magnitude (e.g. from 2 μm 2 To 200μm 2 ) cross section. The channels are present in the nozzle body and are usually manufactured using micro-technical manufacturing techniques such as micro-etching, micro-lithography, etc. However, these techniques are usually targeted at hard and brittle materials such as silicon, glass or metal, and in order to avoid any undesired deformation of the nozzle when subjected to said high pressure, the nozzle is usually made of very rigid material.

[0005] These parts require high precision when manufactured. In particular, inhalers using impact nozzles require that the outflow channels of the microfluidic nozzles be precisely aligned, otherwise the resulting aerosol may not be suitable for inhalation.

[0006] To manufacture nozzles from silicon or glass, a disk-shaped substrate wafer is usually masked and irradiated with a large number of two-dimensional outlines of nozzles or nozzle features (such as channels). The outlines (especially the channels) are then etched vertically into the substrate by selective etching, so that a wafer carrying tens or hundreds of batch-produced semi-finished nozzles exists. In a separation step, the wafer is cut by sawing it into slices representing the individual nozzles with a wafer saw.

[0007] The cutting process can be a source of error and result in a greater number of unusable nozzles or other microfluidic devices. Figure 1B illustrates possible problems. Figure 1A A wafer is illustrated having a plurality of impact nozzle bodies cut or sawn thereon along desired separation lines. Figure 1B A wafer comprising multiple nozzles is shown, which is cut at an angle different from the ideal separation line. This results in an offset of the channel outlets, whereby the distance between the channel outlets differs between the individual nozzles, resulting in different collision points of the aerosol jets, which can potentially affect the quality of the aerosol.

[0008] WO 2019 / 180022 A1 describes a method for producing a nozzle, wherein the nozzle outlet is placed in a recess of the nozzle to compensate for errors of the cutting or sawing process.

[0009] However, the use of recesses is not suitable for every microfluidic device. It can be seen that there is a need for an improved method for manufacturing a microfluidic device with high precision. Summary of the invention

[0010] In a first aspect, the present invention relates to a microfluidic device comprising at least two microfluidic structures, each of which is located at a front end of the microfluidic device; wherein the microfluidic device is at least partially made of single crystal material, and wherein the front end of the microfluidic device and the microfluidic structures are aligned with a crystal orientation line or plane. In some embodiments, the microfluidic device is used in an inhalation device. In a specific embodiment, the microfluidic device is a nozzle for an inhalation device, preferably an impact nozzle.

[0011] In a second aspect, the present invention provides a single crystal wafer comprising a plurality of microfluidic devices according to the first aspect of the present invention.

[0012] In a third aspect, the invention relates to a method for producing a microfluidic device comprising the following steps:

[0013] a) providing a wafer substrate of single crystal material;

[0014] b) fabricating at least one microfluidic device on the wafer substrate, the microfluidic device comprising at least two microfluidic structures, wherein the microfluidic structures are aligned along crystal orientation lines or planes;

[0015] c) separating the microfluidic device (1) from the substrate by cleaving the wafer along crystal orientation lines or planes.

[0016] In a further aspect, the invention relates to the use of a microfluidic device according to the invention, in particular in an inhalation device. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1A and Figure 1B A microfluidic device on a chip is shown. Figure 1A shows the cut along the ideal line, while Figure 1B A non-ideal cut is illustrated.

[0018] Figure 2A Options for cutting wafer disks from a single crystal substrate along different crystal orientation lines are shown.

[0019] Figure 2B The cleavage behavior of single crystal wafers cut with

[100] and

[111] crystal orientations is shown.

[0020] Figure 2C Depicted is the unit cell of the diamond crystal structure.

[0021] Figure 2D A schematic diagram of a diamond crystal structure comprising a plurality of unit cells is shown, with crystal orientation lines therein indicated.

[0022] Figure 3 A simplified example for an impact nozzle is shown.

[0023] Figure 4 A single crystal wafer is shown having a plurality of microfluidic devices, specifically microfluidic nozzles, etched thereon.

[0024] Figure 5 A microfluidic device with a closed device is shown that includes a predetermined breaking point (top) and illustrates how the predetermined breaking point can be used to precisely cleave a single crystal wafer (bottom). DETAILED DESCRIPTION

[0025] The inventors have developed a new method for manufacturing a microfluidic device with high precision using a single crystal material as a basis and an improved microfluidic device based on the method. Therefore, in one aspect, the present invention relates to a microfluidic device, comprising at least two microfluidic structures, each of which is located at the front end of the microfluidic device; characterized in that the microfluidic device is at least partially made of a single crystal material, wherein the front end of the microfluidic device and the microfluidic structure are aligned with the crystal orientation line of the single crystal material.

[0026] In a further aspect, the invention relates to a method for producing a microfluidic device, wherein a microfluidic structure is produced in a single-crystalline wafer and wherein the device is separated from the single-crystalline wafer, for example by breaking or dicing, preferably by breaking.

[0027] Single crystals can be obtained by the Czochralski method. The single crystals obtained by this method can be cut into wafers using a wafer saw. By this high-precision method, wafers can be produced with a maximum deviation of 0.4° (degrees) from the ideal orientation. The wafers can be sliced ​​in different orientations with respect to the unit cell of the single crystal; see Figure 2A It has been found that, depending on the orientation in which the single crystal wafers are cut from the single crystal, the wafer disks show different fracture behaviors; see Figure 2B .

[0028] Figure 2B It is shown that a single crystal wafer obtained from a

[100] oriented cut shows a distinct fracture behavior along the crystal orientation lines. The inventors have found that microfluidic structures can be aligned with said crystal orientation lines to manufacture microfluidic devices with high precision and reproducibility. This allows to reduce misalignment due to the cutting or sawing process and reduce rejects during production.

[0029] The term "crystal orientation line" as used in the context of the present invention refers to the boundaries of a unit cell of a crystal in the corresponding orientation of a single crystal. Figure 2C and Figure 2D Exemplary crystal orientation lines of a single crystal of a diamond structure are illustrated. In a top view of the wafer, the wafer corresponds to a single crystal plane, such as a

[100] plane. It can be seen that in a top view, the

[010] and

[001] crystal orientation planes are substantially visible as single lines. Thus, in a top view of the wafer, the crystal orientation lines correspond to crystal orientation planes that are perpendicular to the plane in which the wafer was cut.

[0030] Thus, a single crystal wafer produced in a

[100] orientation can be cleaved along its crystal orientation line in a

[010] or

[001] orientation and will produce a clean cut along the orientation line.

[0031] Therefore, the present invention also relates to a method for producing a microfluidic device comprising at least two microfluidic structures, the method comprising the following steps:

[0032] a) providing a wafer substrate of single crystal material;

[0033] b) fabricating at least one microfluidic device on the wafer substrate, the microfluidic device comprising at least two microfluidic structures, each of the structures being located at a front end of the microfluidic device; wherein the microfluidic structures are aligned with the crystal orientation lines;

[0034] c) separating the microfluidic device (1) from the substrate by cleaving the wafer along the crystal orientation lines.

[0035] Single crystal wafers are cut with a specific crystal orientation so that the surface of the wafer corresponds to the crystal orientation plane.

[0036] The inventors have discovered that aligning the microfluidic structures of a microfluidic device with a crystal orientation and then cleaving along the crystal orientation lines to separate the device from the substrate allows for high precision manufacturing with reduced rejects compared to cutting or sawing.

[0037] The term "microfluidic structure" used in the context of the present invention refers to any type of microfluidic structure. Preferred microfluidic structures include, but are not limited to, microfluidic chambers or reservoirs, and microfluidic channels. Microfluidic structures also include specific structures, such as microfluidic filter structures. Microfluidic structures also include microfluidic structures that may include additional components that are not part of the single crystal wafer substrate, such as microfluidic valves or mixing chambers.

[0038] In certain embodiments, at least two microfluidic structures are microfluidic channels. In certain embodiments, at least two microfluidic structures are microfluidic channels comprising a microfluidic channel outlet. In a more preferred embodiment, the microfluidic channel outlet is located at the front end of the device.

[0039] In the context of the present invention, the term "alignment" or "aligning a microfluidic structure with a crystal orientation line" refers to positioning the microfluidic structure relative to the crystal orientation line. A crystal orientation line or, in some embodiments, a plurality of crystal orientation lines are reference lines for the microfluidic device. This includes, for example, that a distance measured with reference to the microfluidic structure is measured with reference to the crystal orientation line. For example, the distance of two microfluidic channel outlets is measured based on the crystal orientation line. Alternatively or additionally, the angle of the channel can be measured relative to the crystal orientation line.

[0040] Since microfluidic wafers can be easily and precisely cleaved at crystal orientation lines, aligning the front end of a microfluidic structure or microfluidic device with the crystal orientation lines allows high-precision production with improved reproducibility and a reduced number of rejects.

[0041] Therefore, in a preferred embodiment of the invention, the front end of the microfluidic device is aligned with or follows the crystal orientation line.Preferably, the front end of the device follows the crystal orientation line.

[0042] The single crystal wafer is preferably a single crystal wafer obtained by cutting a single crystal according to the Czochralski process. In a specific embodiment, the single crystal wafer is a single crystal obtained from a material crystallized in a diamond or perovskite crystal structure. Suitable materials are known to the skilled person and include, but are not limited to, single crystal silicon, single crystal germanium or single crystal gallium arsenide. In a preferred embodiment, the single crystal material is single crystal silicon.

[0043] For optimal cleavage characteristics, wafers were cut from a single crystal obtained by the Czochralski method and cut along the

[100] crystal orientation. As shown in Figure 2, wafers cut from a single crystal with a

[100] orientation show ideal cleavage behavior along the crystal orientation lines.

[0044] Corresponding single-crystal wafers are commercially available, for example from Samsung in South Korea or Micron in the USA.

[0045] In many cases, suitable single crystal wafers are circular and have one or two flat sides. Figure 4 In summary, the flat side (7) of the wafer (6) corresponds to the crystal orientation line of the wafer. All other corresponding crystal orientation lines will be perpendicular or parallel to the flat side of the wafer.

[0046] Thus, in a preferred embodiment of the present invention, the single crystal wafer is a

[100] crystal oriented wafer, and the front end of the microfluidic device is aligned with or corresponds to a

[010] or

[001] crystal orientation line. In a preferred embodiment, the wafer is a round wafer including a flat side that corresponds to the crystal orientation line. In some embodiments, the wafer includes a notch indicating the crystal orientation line, which can be used as a predetermined breaking point.

[0047] In some embodiments of the present invention, the wafer substrate of step a) of the method of the present invention is a wafer substrate cut from a single crystal with a

[100] crystal orientation, and the wafer substrate comprises a flat side surface corresponding to a crystal orientation line.

[0048] The wafer can be as thick or thin as desired. In a preferred embodiment, the thickness of the wafer is about 2 mm or less, such as between about 125 μm and about 2 mm. In some embodiments, the thickness of the single crystal wafer is less than 1.5 mm, such as between about 250 μm and about 1.5 mm. In some embodiments, the thickness is 1 mm or less. In a preferred embodiment, the thickness is about 750 μm or less, such as between about 300 μm and about 750 μm.

[0049] The microfluidic device can be manufactured on the wafer by any suitable means. The skilled person knows suitable means for manufacturing a microfluidic device on a single crystal wafer. The method may include chemical or mechanical methods. In some embodiments, the microfluidic device is manufactured by etching the microfluidic device into a single crystal wafer. In some embodiments, the microfluidic device is manufactured by laser etching or laser ablation. In various embodiments, the microfluidic device is manufactured by sandblasting. In some embodiments, the microfluidic device is manufactured by microlithography. In some embodiments, the microfluidic device is manufactured by a combination of different methods (e.g., a combination of etching and laser ablation).

[0050] In addition to the front end aligned with or corresponding to the crystal orientation line, the microfluidic device may include at least one rear end and at least one side end. The microfluidic device may generally have any shape as long as at least one side (ie, the front end) is aligned with the crystal orientation line.

[0051] In a preferred embodiment, the microfluidic device is rectangular and includes a front end, a rear end and two side ends. In a more preferred embodiment, the rear end is aligned with a crystal orientation line parallel to the front end of the microfluidic device, and each side end is aligned with or corresponds to another crystal orientation line perpendicular to the rear end crystal orientation line. In such an embodiment, the method preferably includes the following steps:

[0052] At least one microfluidic device is manufactured on the single crystal wafer, the microfluidic device comprising at least two microfluidic structures, wherein the microfluidic structures are aligned along the crystal orientation; and wherein the front end and the rear end of the device are parallel and aligned, and each corresponds to the crystal orientation line; optionally, wherein the side ends are perpendicular to the front end and the rear end, and each is aligned with and corresponds to the crystal orientation line perpendicular to the crystal orientation line of the front end and the rear end.

[0053] The method is also suitable for mass production of microfluidic devices with high precision. It can be seen that the method can include manufacturing multiple microfluidic devices on a single single crystal wafer. The microfluidic devices can be identical or different. Preferably, the single crystal wafer includes multiple identical microfluidic devices, which are aligned in parallel and their respective rear and side ends are aligned with the crystal orientation lines to allow easy separation; see for example Figure 4 .

[0054] Therefore, in some embodiments, the method of the present invention is a method for producing a plurality of microfluidic devices, each device comprising at least two microfluidic structures, the method comprising the following steps:

[0055] a) providing a wafer substrate of single crystal material;

[0056] b) manufacturing a plurality of microfluidic devices on the wafer substrate, each microfluidic device comprising at least two microfluidic structures, each of the structures being located at a front end of a corresponding microfluidic device; wherein the microfluidic structure of each device is aligned with the crystal orientation line;

[0057] c) separating the microfluidic device (1) from the substrate by cleaving the wafer along the crystal orientation lines.

[0058] In a preferred embodiment, the wafer substrate of step a) of the method of the present invention is a wafer substrate cut from a single crystal material with a

[100] crystal orientation, and the wafer substrate comprises flat side surfaces corresponding to the crystal orientation lines.

[0059] In a preferred embodiment of the present invention, the front end of each of the plurality of microfluidic devices is aligned with the crystal orientation line.

[0060] Therefore, in some embodiments of the present invention, the chip substrate is a chip substrate as defined above, and step b) of the method includes: manufacturing a plurality of microfluidic devices on the chip substrate, each microfluidic device comprising at least two microfluidic structures, each of the structures being located at the front end of the corresponding microfluidic device; wherein the microfluidic structures are aligned with the crystal orientation lines; and wherein the front end of at least one of the plurality of microfluidic devices is aligned with or preferably corresponds to the flat side of the single crystal chip substrate.

[0061] The method of the present invention is particularly suitable for large-scale production of rectangular microfluidic devices. Therefore, in some embodiments, the present invention relates to a method for producing a plurality of microfluidic devices as defined above, wherein the microfluidic devices comprise at least two microfluidic structures and each microfluidic device comprises a front end, a rear end and two side ends. In a preferred embodiment, the rear end is parallel to the front end of the device and the side ends are perpendicular to the front end and the rear end.

[0062] Thus, in some embodiments, the present invention relates to a method for producing a plurality of microfluidic devices as defined above, wherein each microfluidic device comprises a front end, a rear end and two side ends, wherein the rear end of the microfluidic device is parallel to the front end of the device and the side ends of the microfluidic device are perpendicular to the front end and the rear end of the microfluidic device, the method comprising the following steps:

[0063] a) providing a wafer substrate of single crystal material;

[0064] b) fabricating a plurality of microfluidic devices on the wafer substrate, each microfluidic device comprising at least two microfluidic structures, each of the structures being located at a front end of a corresponding microfluidic device; wherein the microfluidic structures are aligned with the crystal orientation lines; wherein the plurality of microfluidic devices are fabricated in a checkerboard pattern, wherein the microfluidic devices are positioned parallel to each other such that a first row of microfluidic devices comprises front ends aligned with the crystal orientation lines, parallel rear ends aligned with different parallel crystal orientation lines, and side ends aligned with perpendicular crystal orientation lines, wherein a side end of one microfluidic device is adjacent to a side end of another microfluidic device, and a rear end of a microfluidic device is adjacent to a front end of a microfluidic device;

[0065] c) Separating the microfluidic devices (1) from the substrate and from each other by cleaving the wafer along the crystal orientation lines.

[0066] The microfluidic devices may be identical or different microfluidic devices. Preferably, the microfluidic devices are identical.

[0067] One or more microfluidic devices may be cleaved from a wafer by any suitable method. The skilled person is aware of suitable methods for cleaving a wafer at a crystal orientation line. Suitable methods include cutting and breaking or a combination thereof. In a preferred embodiment, cleaving comprises breaking the microfluidic device from the microfluidic wafer at the crystal orientation line. The breaking may be done manually or by machine. In order to improve the cleavage accuracy of a single crystal wafer, the wafer may be covered with a plate comprising predetermined breaking points or breaking lines adapted to the wafer, wherein the breaking points or breaking lines are adapted to the crystal orientation lines of the single crystal wafer. In such an embodiment, the plate having predetermined breaking points or breaking lines will be cleaved, in particular broken, together with the single crystal wafer.

[0068] In some embodiments, the wafer may include predetermined break lines or break points. The wafer may be slightly shaved or indented at predetermined portions to produce the predetermined break points. The predetermined break points may also be added during the process of manufacturing the microfluidic device into the wafer. For example, the predetermined break points or break lines may be etched into the wafer. Such predetermined break points or break lines may be manufactured by the same methods as the microfluidic device, for example by etching, in particular laser etching, laser ablation, sandblasting or microlithography.

[0069] In some embodiments, before or after cleavage, the microfluidic device is covered with a closure device. The closure device preferably seals and closes the microfluidic structure. In some embodiments, the closure device corresponds to a lid. In some embodiments, the closure device corresponds to a cover.

[0070] The closure device may be permanently attached to the microfluidic device, for example by using glue or atomic bonding. In some embodiments, the closure device is placed on the microfluidic device and held in place by a separate holding structure.

[0071] In a preferred embodiment, the closure covers the single crystal wafer and comprises a predetermined cleavage site (5) aligned with the crystal orientation line of the wafer. In this case, the predetermined cleavage site of the closure may be adapted to cleave the microfluidic device of the closure and the wafer; see Figure 5 .

[0072] The method according to the invention is particularly suitable for producing microfluidic nozzles, preferably nozzles for use in inhalation devices, in particular impact nozzles. Figure 3 An exemplary impact nozzle is shown in FIG.

[0073] In an impact nozzle, a fluid is ejected through two ejection channels (2, 2'), each having a channel outlet (2A, 2A') at the front end of the nozzle. The channels and the channel outlets are arranged to eject the liquid along respective ejection trajectories, wherein the ejection trajectories intersect each other at a collision point. The collision of the two fluid streams at the collision point generates an inhalable aerosol.

[0074] In order to provide an ideal inhalable aerosol, the jet trajectory and distance of the outlet channel must be precisely defined. If the nozzle is produced according to the method of the present invention and the jet channel is aligned with the crystal orientation line, the number of discarded nozzles can be reduced because the number of nozzles that cannot be used due to incorrect cutting or sawing is reduced.

[0075] Therefore, in a particular embodiment, the present invention relates to a method for producing a microfluidic device as defined above, wherein the microfluidic device is a nozzle of an inhalation device for atomizing a liquid into an inhalable aerosol, having a nozzle body (1) having a front end (1B), and wherein at least two microfluidic structures are ejection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), wherein the ejection channels (2, 2') are arranged to eject liquid along respective ejection trajectories, wherein the ejection trajectories intersect each other at a collision point, and wherein

[0076] The nozzle body (1) has a flat side surface (1A), wherein at least two liquid channels (2, 2') are embedded in the flat side surface (1A) with a defined depth (D), and the nozzle body has a front end (4B) which, in a view perpendicular to the longitudinal axis (X) of the nozzle body (1), coincides with the front end (1B) of the nozzle body (1),

[0077] wherein the nozzle body is at least partially made of a single crystal material, and the channel outlets of the respective injection channels are positioned in accordance with the crystal orientation so that the collision point is on the longitudinal axis (X) of the nozzle body;

[0078] The method comprises the following steps:

[0079] a) preparing a nozzle body (1) having a front end (1B) and comprising at least two injection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), wherein the injection channels (2, 2') are arranged to inject liquid along corresponding injection trajectories, the injection trajectories intersecting each other at a collision point on the longitudinal axis (X), wherein the nozzle body (1) has a flat side surface (1A), wherein at least two liquid channels (2, 2') are embedded in the flat side surface (1A) at a defined depth (D), the step comprising the following steps:

[0080] (i) providing a wafer substrate of single crystal material;

[0081] (ii) manufacturing a nozzle body comprising at least two liquid channels (2, 2') on one side (1A) of the substrate, the channels (2, 2') having a defined depth (D), wherein the liquid channel outlets are aligned along a crystal orientation;

[0082] (iii) separating the body (1) from the substrate by cleaving the wafer along crystal orientation lines;

[0083] b) Optionally covering the nozzle body (1) with a closure device (3).

[0084] In some embodiments of the invention, the channel outlets are made on the crystal orientation lines so as to eject the liquid along corresponding ejection trajectories, wherein the ejection trajectories intersect each other at collision points on the longitudinal axis (X). Preferably, the channel outlets are each equidistant from the longitudinal axis.

[0085] In particular, the method is suitable for producing a plurality of microfluidic nozzles as defined above.

[0086] In a preferred embodiment, the nozzle is covered by a closure, preferably a cap. In some embodiments, the closure is a cover. The closure may be of the same or different material than the nozzle. In some embodiments, the closure is of a different material. In a particular embodiment, the closure is made of glass.

[0087] In some embodiments, the single crystal wafer is covered by a cap wafer and the wafer is cleaved together with the cap wafer. In a preferred embodiment, the cleaved cap wafer is held on the cleaved nozzle to obtain a nozzle covered with a closure device. In some embodiments, the cap wafer comprises a predetermined breaking point which is aligned with a crystal orientation line of the single crystal wafer and the nozzle manufactured on the single crystal wafer.

[0088] The nozzles produced by the method of the present invention show higher precision and reproducibility of aerosol quality.

[0089] Typically, a microfluidic device produced using the method according to the invention requires less material overall, since the additional space required as a safety measure to accommodate inaccuracies can be reduced. Typically, the number of rejects of microfluidic devices can be reduced using this method.

[0090] In addition to this method, in a specific second aspect, the present invention relates to a single crystal wafer comprising a plurality of microfluidic devices as defined above, wherein each of the microfluidic devices comprises at least two microfluidic structures, each of the structures being located at the front end of the microfluidic device; and wherein the front end of the microfluidic device and the microfluidic structures are aligned with the crystal orientation lines. Figure 4 An example of such a wafer is shown in .

[0091] The single crystal wafer including the plurality of microfluidic devices is preferably a wafer substrate cut from a single crystal with a

[100] crystal orientation, and the wafer substrate includes flat side surfaces corresponding to the crystal orientation lines.

[0092] The single crystal wafer comprising a plurality of microfluidic devices according to this aspect of the invention is preferably a single crystal wafer obtained by cutting a single crystal according to the Czochralski method. In particular, the single crystal wafer comprising a plurality of microfluidic devices is a single crystal obtained from a material crystallized in a diamond or perovskite crystal structure. Suitable materials are known to the skilled person and include, but are not limited to, single crystal silicon, single crystal germanium or single crystal gallium arsenide. In a preferred embodiment, the single crystal material is single crystal silicon.

[0093] In a preferred embodiment, the plurality of microfluidic devices are arranged in a parallel orientation. The plurality of microfluidic devices can be manufactured on a wafer by any suitable means as described above. Suitable means include, but are not limited to, etching, laser etching, laser ablation, sandblasting, and microlithography.

[0094] In a specific embodiment, the microfluidic device included on the single crystal wafer includes a front end, a rear end, and two side ends, wherein the device is aligned so that the front end of the device is aligned with a first crystal orientation line, the rear end is aligned with a second crystal orientation line parallel to the first crystal orientation line, and the side ends are aligned with crystal orientation lines perpendicular to the first crystal orientation line and the second crystal orientation line, so that the microfluidic device can be separated by cutting or breaking along the crystal orientation lines.

[0095] In a specific embodiment, a plurality of microfluidic devices included on a single crystal wafer are arranged in a checkerboard pattern, wherein the rear end of one device is in contact with the front end of another device and the side end of one device. It can be seen that the wafer allows obtaining a plurality of microfluidic devices by cleaving the devices along corresponding crystal orientation lines. In particular, the microfluidic devices are obtained by breaking the devices at the corresponding crystal orientation lines.

[0096] Therefore, in a further aspect, the present invention relates to a microfluidic device obtainable by a method as described above. In particular, the present invention relates to a microfluidic nozzle obtainable by a method as defined above.

[0097] Thus, in one aspect, the present invention relates to a microfluidic device comprising at least two microfluidic structures, each of said structures being located at the front end of the microfluidic device; characterised in that the microfluidic device is at least partially made of a single crystalline material, and wherein said front end of the microfluidic device and the microfluidic structures are aligned with a crystal orientation line of the single crystalline material. Preferably, the front end of the device is on the crystal orientation line.

[0098] In particular, said front end of the microfluidic device follows or corresponds to a crystal orientation line of a single crystalline material.Most preferably, the front end of the microfluidic device is obtained by cleaving said device from a single crystalline wafer at the crystal orientation line.

[0099] The single crystal material of the microfluidic device preferably corresponds to a single crystal material obtained from a single crystal sliced ​​on one crystal plane. More preferably, the single crystal material is a single crystal material obtained from a single crystal sliced ​​with a

[100] crystal orientation, and the crystal orientation line to which the front end of the microfluidic device is aligned corresponds to a

[010] or

[001] crystal orientation line.

[0100] Aligning the microfluidic structure with the crystal orientation line allows to obtain a reproducible microfluidic device in an easy and simple manner. Any type of microfluidic structure is suitable. Preferably, the microfluidic structure is fixed on the chip. Preferred microfluidic structures include but are not limited to microfluidic chambers or reservoirs and microfluidic channels. The microfluidic structure also includes a specific structure, such as a microfluidic filter structure. The microfluidic structure also includes a microfluidic structure, which may include additional components that are not a part of a single crystal wafer substrate, such as a microfluidic valve or a mixing chamber.

[0101] In particular, a microfluidic structure comprising a microfluidic channel having a microfluidic channel outlet is preferred. Alignment along the crystal orientation lines allows precise positioning, and when the device is cleaved along the crystal orientation lines, the precise positioning is not affected by, for example, inaccurate cutting or sawing. Preferably, the microfluidic structure is present in (e.g. etched into) a single crystal material.

[0102] The skilled person is aware of suitable single crystal materials. Preferably, the single crystal material is a material crystallized in a diamond crystal structure or a perovskite crystal structure. Preferred materials for microfluidic devices include single crystal silicon, single crystal germanium or single crystal gallium arsenide. In a preferred embodiment, the single crystal material is single crystal silicon.

[0103] The microfluidic device according to the present invention preferably comprises a front end and a rear end. The microfluidic device also comprises two or more side ends, however preferably, the device comprises two side ends and is generally rectangular in shape. However, the microfluidic device is not limited to a rectangular shape.

[0104] Single crystal materials allow for small and compact microfluidic devices with reduced thickness. In some embodiments, a microfluidic device according to the present invention has a thickness of about 1.5 mm or less. In a preferred embodiment, the thickness of the microfluidic device is less than 1.5 mm, for example, it has a thickness of about 250 μm to about 1.5 mm. In some embodiments, the thickness is about 1 mm or less. In a preferred embodiment, the thickness is about 750 μm or less, for example, between about 300 μm and about 750 μm.

[0105] At least two microfluidic structures preferably include a microfluidic channel, which includes a microfluidic channel outlet. The channel outlet can be positioned with high precision, which ensures compatibility with other devices, for example, for transferring fluid from one device to another. Compared with microfluidic devices obtained by cutting or sawing, the microfluidic device according to the present invention shows high precision, thereby reducing the number of incompatible devices due to misaligned cutting or sawing.

[0106] In a preferred embodiment, the microfluidic device comprises a microfluidic channel and a microfluidic channel outlet, and the microfluidic channel outlet is located at the front end of the microfluidic device and aligned with the crystal orientation line.

[0107] The microfluidic device can be any type of microfluidic device. In some embodiments, the microfluidic device is an open microfluidic device. In some embodiments, the microfluidic device is at least partially closed. In some embodiments, the microfluidic device includes a closure device that covers at least a portion of the device. In some embodiments, the device includes a closure device that covers a microfluidic structure. In some embodiments, the microfluidic device includes a closure device that covers part or all of the device. The closure device can be a cover. In some embodiments, the closure device is a cover.

[0108] If the device includes a closure, the closure may be made of any material. In some embodiments, the closure is made of the same single crystal material. In some embodiments, the closure is made of different materials. Any material suitable for microfluidic applications may be used. Suitable materials are known to the skilled person. In some embodiments, wherein the microfluidic device includes a closure, the closure is made of glass.

[0109] Microfluidic device according to the present invention can be any microfluidic device that needs high precision.In a preferred embodiment of the present invention, microfluidic device is used for suction device.In certain embodiments, microfluidic device is or comprises valve or is part of valve.In other embodiments, microfluidic device is or comprises filter unit.In certain embodiments, microfluidic device according to the present invention is nozzle for suction device.In a specific embodiment, microfluidic device according to the present invention is impact nozzle.

[0110] Therefore, in a specific embodiment, the present invention relates to a microfluidic nozzle, wherein the nozzle is a nozzle of an inhalation device for atomizing a liquid into an inhalable aerosol, having a nozzle body (1) having a front end (1B), and wherein at least two microfluidic structures are ejection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), wherein the ejection channels (2, 2') are arranged to eject liquid along respective ejection trajectories intersecting each other at a collision point, wherein

[0111] The nozzle body (1) has a flat side surface (1A), wherein at least two liquid channels (2, 2') are embedded in the flat side surface (1A) with a defined depth (D), and the flat side surface has a front end (4B) which, in a view perpendicular to the longitudinal axis (X) of the nozzle body (1), coincides with the front end (1B) of the nozzle body (1),

[0112] The invention is characterized in that the nozzle body is made of a single crystal material, and the channel outlets of the respective injection channels are positioned in accordance with the crystal orientation so that the collision point is on the longitudinal axis of the nozzle body.

[0113] In a preferred embodiment of the present invention, the microfluidic channel outlet of the injection channel is on the crystal orientation line of the single crystal material.

[0114] The single crystal material of the nozzle preferably corresponds to a single crystal material obtained from a single crystal sliced ​​on one crystal plane. More preferably, the single crystal material is a single crystal material obtained from a single crystal sliced ​​with a

[100] crystal orientation, and the crystal orientation line to which the front end of the microfluidic device is aligned corresponds to a

[010] or

[001] crystal orientation line.

[0115] In some embodiments, the nozzle comprises a closure, preferably a cap. In some embodiments, the closure is a cover. The closure may be made of the same material as the nozzle or a different material. In some embodiments, the closure is made of glass.

[0116] The invention also relates to the use of a microfluidic device obtained by a process as defined above as a nozzle in an inhalation device for atomizing a liquid into an inhalable aerosol.

[0117] In a particular aspect, the present invention also relates to an inhalation device for atomizing a liquid into an inhalable aerosol, comprising at least one microfluidic device as defined above, in particular a nozzle as defined above.

[0118] All embodiments described above with respect to the method of the invention apply to all aspects of the invention, including the microfluidic device according to the invention and the single-crystal wafer according to the invention.

[0119] The present invention also relates to the following numbered items:

[0120] 1. A microfluidic device comprising at least two microfluidic structures, each of which is located at the front end of the microfluidic device; characterized in that the microfluidic device is at least partially made of single crystal material, and wherein the front end of the microfluidic device and the microfluidic structures are aligned with the crystal orientation lines of the single crystal material.

[0121] 2. A microfluidic device according to item 1, wherein the microfluidic structure is a microfluidic channel comprising a microfluidic channel outlet.

[0122] 3. A microfluidic device according to item 2, wherein the microfluidic channel outlet is located at the front end of the microfluidic device and is aligned with the crystal orientation line.

[0123] 4. A microfluidic device according to any one of items 1 to 3, wherein the microfluidic device is made of a single crystal material, wherein the material is crystallized in a diamond cubic crystal structure or a perovskite crystal structure.

[0124] 5. A microfluidic device according to any one of items 1 to 4, wherein the single crystal material is selected from silicon, germanium and gallium arsenide.

[0125] 6. A microfluidic device according to any one of items 1 to 5, wherein the microfluidic structure is present in a single crystalline material.

[0126] 7. A microfluidic device according to any one of items 1 to 6, wherein the microfluidic device comprises a closing device.

[0127] 8. A microfluidic device according to item 7, wherein the closing means is made of the same single crystal material.

[0128] 9. A microfluidic device according to item 7, wherein the closing means are made of different materials.

[0129] 10. A microfluidic device according to item 9, wherein the sealing device is made of glass.

[0130] 11. The microfluidic device according to any one of items 1 to 10, wherein the microfluidic device is a nozzle.

[0131] 12. A microfluidic device according to item 11, wherein the nozzle is an impact nozzle.

[0132] 13. A microfluidic device according to claim 12, wherein the nozzle is a nozzle of an inhalation device for atomizing a liquid into an inhalable aerosol, having a nozzle body (1) having a front end (1B), and wherein at least two microfluidic structures are injection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), wherein the injection channels (2, 2') are arranged to inject liquid along corresponding injection trajectories that intersect each other at a collision point, wherein,

[0133] The nozzle body (1) has a flat side surface (1A), wherein at least two liquid channels (2, 2') are on the flat side surface (1A), and the flat side surface has a front end (3B) which, in a view perpendicular to the longitudinal axis (X) of the nozzle body (1), coincides with the front end (1B) of the nozzle body (1),

[0134] The invention is characterized in that the nozzle body is made of a single crystal material, and the channel outlets of the respective injection channels are positioned in accordance with the crystal orientation so that the collision point is on the longitudinal axis of the nozzle body.

[0135] 14. A microfluidic device according to item 13, wherein the nozzle includes a closure device.

[0136] 15. A single crystal wafer comprising a plurality of microfluidic devices according to any one of items 1 to 14.

[0137] 16. A single crystal wafer according to item 15, wherein a plurality of microfluidic devices are arranged in a parallel orientation.

[0138] 17. A single crystal chip according to item 16, wherein the microfluidic device includes a front end, a rear end and two side ends, wherein the device is aligned so that the front end of the device is aligned with a first crystal orientation line, the rear end is aligned with a second crystal orientation line parallel to the first crystal orientation line, and the side ends are aligned with crystal orientation lines perpendicular to the first crystal orientation line and the second crystal orientation line, so that the microfluidic device can be separated by cutting or breaking along the crystal orientation lines.

[0139] 18. A single crystal wafer according to item 17, wherein a plurality of microfluidic devices are arranged in a checkerboard pattern, wherein a rear end of one device contacts a front end of another device, and a side end of one device contacts a side end of another device.

[0140] 19. A method for producing a microfluidic device according to any one of items 1 to 14, comprising the steps of:

[0141] a) providing a wafer substrate of single crystal material;

[0142] b) fabricating at least one microfluidic device on the wafer substrate, the microfluidic device comprising at least two microfluidic structures, wherein the microfluidic structures are aligned along a crystal orientation;

[0143] c) separating the microfluidic device (1) from the substrate by cleaving the wafer along the crystal orientation lines.

[0144] 20. A method for producing a microfluidic device according to item 19, wherein the method comprises etching the microfluidic structure of the device into a wafer.

[0145] 21. A method for producing a microfluidic device, wherein the microfluidic device is a nozzle for an inhalation device according to any one of items 12 to 14, the method comprising the following steps:

[0146] a) preparing a nozzle body (1) having a front end (1B) and comprising at least two injection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), wherein the injection channels (2, 2') are arranged to inject liquid along corresponding injection trajectories, the injection trajectories intersecting each other at a collision point, wherein at least one recess (3) is provided at the front end (1B), at least two of the channel outlets (2A, 2A') being positioned in the recess, wherein the nozzle body (1) has a flat side surface (1A), wherein at least two liquid channels (2, 2') are embedded in the flat side surface (1A) at a defined depth (D), the step comprising the following steps:

[0147] (i) providing a wafer substrate of single crystal material;

[0148] (ii) manufacturing at least two liquid channels (2, 2') on one side (1A) of the substrate, the channels (2, 2') having a defined depth (D), wherein the liquid channel outlets are aligned along the crystal orientation;

[0149] (iii) separating the body (1) from the substrate by cleaving the wafer along crystal orientation lines;

[0150] b) Optionally covering the nozzle body (1) with a closure means.

[0151] 22. A nozzle for an inhalation device obtainable by a method according to item 21.

[0152] 23. Use of a microfluidic device according to any one of items 12 to 14 as a nozzle in an inhalation device for atomizing a liquid into an inhalable aerosol.

[0153] 24. An inhalation device for atomizing a liquid into an inhalable aerosol, comprising at least one microfluidic device according to any one of items 1 to 14.

[0154] Label list

[0155] 1 Nozzle body

[0156] 1A Flat side

[0157] 1B front end

[0158] 2.2' injection channel, liquid channel, channel

[0159] 2A, 2A' channel exit

[0160] 2B, 2B' front channel exit

[0161] 3 Closure device

[0162] 4 separation line

[0163] 4' Optimal separation line

[0164] 5Predetermined cleavage location

[0165] 6Single crystal wafer

[0166] 7Flat side of the wafer

[0167] A, A' jet axis

[0168] X longitudinal axis

[0169] Y, Y' horizontal distance

[0170] D Depth

Claims

1. A microfluidic device comprising at least two microfluidic structures, each of which is located at the front end of the microfluidic device; characterized in that: The microfluidic device is at least partially made of a single crystal material, and wherein the front end of the microfluidic device and the microfluidic structure are aligned with crystal orientation lines of the single crystal material; wherein the microfluidic device is a nozzle for an inhalation device.

2. The microfluidic device according to claim 1, wherein The microfluidic structure is a microfluidic channel including a microfluidic channel outlet, wherein the microfluidic channel outlet is located at the front end of the microfluidic device and is aligned with the crystal orientation line.

3. The microfluidic device according to any one of claims 1 or 2, wherein The microfluidic device is made of a single crystal material, wherein the material is crystallized in a diamond cubic crystal structure or a perovskite crystal structure.

4. The microfluidic device according to any one of claims 1 to 3, wherein: The microfluidic device is made of a single crystal material, wherein the single crystal material is selected from silicon, germanium and gallium arsenide.

5. The microfluidic device according to any one of claims 1 to 4, wherein The microfluidic device includes a closure.

6. The microfluidic device according to claim 5, wherein The closure device is made of glass.

7. The microfluidic device according to any one of claims 1 to 6, wherein: The nozzle is an impact nozzle.

8. The microfluidic device according to claim 7, wherein The nozzle is a nozzle of an inhalation device for atomizing a liquid into an inhalable aerosol, having a nozzle body (1), the nozzle body having a front end (1B), and wherein at least two microfluidic structures are injection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), wherein the injection channels (2, 2') are arranged to inject liquid along corresponding injection trajectories, the injection trajectories intersecting each other at a collision point, wherein The nozzle body (1) has a flat side surface (1A), wherein the at least two liquid channels (2, 2') are on the flat side surface (1A), and the flat side surface has a front end (4B), and in a view perpendicular to the longitudinal axis (X) of the nozzle body (1), the front end of the flat side surface overlaps with the front end (1B) of the nozzle body (1), And wherein the nozzle body is made of a single crystal material having a crystal orientation line, and wherein the channel outlet of each injection channel is positioned in accordance with the crystal orientation so that the collision point is on the longitudinal axis of the nozzle body.

9. A single crystal wafer comprising a plurality of microfluidic devices according to any one of claims 1 to 8, wherein: The microfluidic device is a nozzle for an inhalation device.

10. The single crystal wafer according to claim 9, wherein: The wafer comprises: - a first crystal orientation line; - a second crystal orientation line parallel to said first crystal orientation line; and - a plurality of crystal orientation lines which are perpendicular to the first crystal orientation line and the second crystal orientation line, and Wherein, the microfluidic device comprises: -front end; -rear end; - two side ends, wherein the device is aligned so that the front end of the device is aligned with the first crystal orientation line of the chip, the rear end is aligned with the second crystal orientation line of the chip, and the side end is aligned with the crystal orientation line of the chip, the crystal orientation line being perpendicular to the first crystal orientation and the second crystal orientation.

11. The single crystal wafer according to claim 9 or 10, wherein: The plurality of microfluidic devices are arranged in a checkerboard pattern, wherein the rear end of one device contacts the front end of another device, and the side end of one device contacts the side end of another device.

12. A method for producing a microfluidic device, wherein: The microfluidic device is a nozzle for an inhalation device according to any one of claims 6 to 8, and the method comprises the following steps: a) preparing a nozzle body (1), the nozzle body having a front end (1B) and comprising at least two injection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), wherein the injection channels (2, 2') are arranged to inject liquid along corresponding injection trajectories, the injection trajectories intersecting each other at a collision point, wherein at least one recess (3) is provided at the front end (1B), at least two of the channel outlets (2A, 2A') being positioned in the recess, wherein the nozzle body (1) has a flat side surface (1A), wherein the at least two liquid channels (2, 2') are embedded in the flat side surface (1A) at a defined depth (D), the step comprising the following steps: (i) providing a wafer substrate of a single crystal material having crystal orientation lines; (ii) manufacturing at least two liquid channels (2, 2') on one side (1A) of the substrate, the channels (2, 2') having a defined depth (D), wherein the liquid channel outlets are aligned along the crystal orientation lines; (iii) separating the body (1) from the wafer substrate by cleaving the wafer along the crystal orientation lines; b) Optionally covering the nozzle body (1) with a closure means.

13. The method according to claim 11 or 12, wherein: The step of separating the microfluidic device from the wafer substrate is performed by breaking the microfluidic device from the wafer substrate.

14. Use of a microfluidic device according to any one of claims 6 to 8 as a nozzle in an inhalation device for atomizing a liquid, preferably a medically active liquid, into an inhalable aerosol.

15. An inhalation device for atomizing a liquid into an inhalable aerosol, comprising at least one microfluidic device according to any one of claims 1 to 8.

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