Microfluidic device and production method

Abstract

The present invention provides a microfluidic device (1) comprising at least two microfluidic structures (2A, 2A'), specifically a nozzle for an inhalation device, each of said structures (2A, 2A') being located at the front end portion (1B) of the microfluidic device, the microfluidic device (1) being at least partially made of a single crystal material, and the front end portion (1B) of the microfluidic device (1) and the microfluidic structures (2A, 2A') being aligned with a crystal orientation line, as well as a method for producing said device and its use.

Description

Technical Field

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

Background Art

[0002] Microfluidic devices are important components of many medical and scientific devices. For example, nebulizers and other aerosol generators utilize a plurality of microfluidic devices, in particular nozzles, valves, and pump systems.

[0003] Nebulizers or other aerosol generators for liquids have long been known in the art. In particular, such devices are used in medicine and therapy. There, they function as inhalation devices for applying an active ingredient in the form of an aerosol, i.e., small liquid droplets embedded in a gas. Such inhalation devices are known, for example, from European Patent No. 0627230. The essential components of this inhalation device are a reservoir for containing the liquid to be aerosolized, a pumping unit for generating a pressure high enough to spray, and an atomizing device in the form of a nozzle.

[0004] In many inhalation devices, the nozzle is a microfluidic nozzle. In order to achieve sufficiently homogeneous and fine mist droplets, relatively high pressures are usually required, such as 10 bar, up to 1000 bar. In order to keep the amount of vaporized liquid per dose acceptably low, the spray nozzle usually comprises one or several channels, each of which is a few μm 2 in size, for example 2 μm 2 ~200 μm 2It has only the cross-section. The channel exists within the nozzle body and is often manufactured using microfabrication techniques such as microetching and microlithography. However, these techniques often target hard and brittle materials such as silicon, glass, or metal, and the nozzle is often made from a very rigid material to avoid unwanted deformation of the nozzle when subjected to the high pressure.

[0005] Components require high precision during manufacturing. In particular, inhalers using impact nozzles require the outflow channels of the microfluidic nozzles to be accurately aligned; otherwise, the resulting aerosol may not be suitable for inhalation.

[0006] To fabricate nozzles from silicon or glass, often a disk-shaped substrate wafer is masked and irradiated with the two-dimensional profile of a number of nozzles, or nozzle features such as channels. Then, by selective etching, the profile, particularly the channel, is etched perpendicular to the substrate, and there is a wafer carrying dozens or hundreds of batch-fabricated semi-finished nozzles. In the separation step, the wafer is cut into pieces representing individual nozzles by sawing with a wafer saw.

[0007] The cutting process can be a source of error and can result in more unusable nozzles or other microfluidic devices. Figure 1B illustrates the possible problems. Figure 1A illustrates a wafer with a plurality of impact nozzle bodies cut or sawn along an ideal separation line. Figure 1B shows a wafer with a plurality of nozzles cut at an angle different from the ideal separation line. This results in an offset at the channel exit, and thus the distance between the channel exits varies between each nozzle, and as a result, the collision points of the aerosol jets are different, potentially affecting the quality of the aerosol.

[0008] WO 2019 / 180022 describes a method for preparing a nozzle in which the nozzle outlet is installed in a recess of the nozzle to compensate for errors in a cutting or sawing process.

[0009] However, using a recess is not suitable for all microfluidic devices. Therefore, an improved manufacturing method for high-precision microfluidic devices is needed.

Prior Art Documents

Patent Documents

[0010]

Patent Document 1

Patent Document 2

Summary of the Invention

[0011] In a first aspect, the present invention relates to a microfluidic device comprising at least two microfluidic structures, each of said structures being located at a front end portion of the microfluidic device, said microfluidic device being at least partially made of a single crystal material, and said front end portion of the microfluidic device and the microfluidic structures being aligned with a crystal orientation line or a crystal orientation plane. In some embodiments, said microfluidic device is used in an inhalation device. In certain embodiments, said microfluidic device is a nozzle for an inhalation device, preferably an impinging nozzle.

[0012] In a second aspect, the present invention provides a single crystal wafer comprising a plurality of microfluidic devices according to a third aspect of the present invention.

[0013] In a third aspect, the present invention relates to a method for producing a microfluidic device, a) providing a wafer substrate of a single crystal material, b) fabricating at least one microfluidic device comprising at least two microfluidic structures on the wafer substrate, wherein the microfluidic structures are aligned along a crystal orientation line or a crystal orientation plane; c) separating the microfluidic device (1) from the substrate by cleaving the wafer along the crystal orientation line or the crystal orientation plane; relates to a method comprising the above steps.

[0014] In a further aspect, the present invention relates to the use of a microfluidic device according to the present invention, particularly in an inhalation device. BRIEF DESCRIPTION OF THE DRAWINGS

[0015]

Figure 1A

Figure 1B

Figure 2A

Figure 2B

[0100] and

[0111] .

Figure 2c

Figure 2D

Figure 3

Figure 4

Figure 5

Best Mode for Carrying Out the Invention

[0016] The inventors of the present invention 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 this method. Thus, in one aspect, the present invention is a microfluidic device comprising at least two microfluidic structures, each of said structures being located at the front end of the microfluidic device, the microfluidic device being at least partially made from a single crystal material, and the front end of the microfluidic device and the microfluidic structures being aligned with the crystal orientation lines of the single crystal material.

[0017] In a further aspect, the present invention is a method for producing a microfluidic device, wherein the microfluidic structure is fabricated within a single crystal wafer and the device is separated from the single crystal wafer, for example, by breaking or cutting, preferably by breaking.

[0018] Single crystals can be obtained by the Czochralski process. The single crystals obtained by this process can be sliced into wafers using a wafer saw. By this high-precision process, wafers can be produced with a derivation of up to 0.4° (degrees) from the ideal orientation. The wafers can be sliced in different orientations with respect to the unit cells of the single crystal. See Figure 2A. It has been found that the wafer disks exhibit different fracture behaviors depending on the orientation in which the single crystal wafer is sliced from the single crystal. See Figure 2B.

[0019] Figure 2B shows that a single crystal wafer obtained from a cut in the

[0100] orientation exhibits a distinct fracture behavior along the crystal orientation lines. The inventors have found that by aligning the microfluidic structures with the crystal orientation lines, a microfluidic device with high precision and reproducibility can be fabricated. This makes it possible to reduce misalignment due to the cutting or sawing process and reduce defective products during production.

[0020] As used in the context of the present invention, the term "crystal orientation line" refers to the boundaries of the unit cell of a crystal in each orientation of a single crystal. FIGS. 2C and 2D illustrate exemplary crystal orientation lines of a single crystal of a diamond structure. In a top view of the wafer, the wafer corresponds to a single crystal plane, for example, the

[0100] plane. Thus, in the top view, the

[0010] and

[0001] crystal orientation planes appear as essentially a single line. Thus, in the top view of the wafer, the crystal orientation line corresponds to a crystal orientation plane perpendicular to the plane in which the wafer is cut.

[0021] Thus, a single crystal wafer produced in the

[0100] orientation can be cleaved along its crystal orientation line in the

[0010] or

[0001] orientation, resulting in a clean and sharp cut along the orientation line.

[0022] Thus, the present invention also relates to a method for producing a microfluidic device comprising at least two microfluidic structures, a) providing a wafer substrate of a single crystal material; b) fabricating at least one microfluidic device comprising at least two microfluidic structures on the wafer substrate, each of the structures being located at the front end of the microfluidic device and the microfluidic structures being aligned with the crystal orientation line; c) separating the microfluidic device (1) from the substrate by cleaving the wafer along the crystal orientation line; and relates to a method.

[0023] The single crystal wafer is cut in a specific crystal orientation such that the surface of the wafer corresponds to a crystal orientation plane.

[0024] The inventors have found that by aligning the microfluidic structures of a microfluidic device with the crystal orientation and then cleaving along the crystal orientation line to separate the device from the substrate, high-precision fabrication with reduced defective products compared to cutting or sawing becomes possible.

[0025] As used in the context of the present invention, the term "microfluidic structure" refers to any kind 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 a single crystal wafer substrate, such as microfluidic valves or mixing chambers.

[0026] In certain embodiments, at least two microfluidic structures are microfluidic channels. In some embodiments, at least two microfluidic structures are microfluidic channels having a microfluidic channel outlet. In a more preferred embodiment, the microfluidic channel outlet is located at the front end of the device.

[0027] In the context of the present invention, the term "aligned" or "aligning the microfluidic structure with the crystal orientation line" refers to positioning the microfluidic structure with respect to the crystal orientation line. The crystal orientation line, or in some embodiments, the crystal orientation line is a reference line of the microfluidic device. This includes, for example, that distances measured with reference to the microfluidic structure are measured with reference to the crystal orientation line. For example, the distance between two microfluidic channel outlets is measured and is based on the crystal orientation line. Alternatively or additionally, the angle of the channel may be measured with respect to the crystal orientation line.

[0028] Since the microfluidic wafer can be easily and accurately cleaved along the crystal orientation line, aligning the front end of the microfluidic structure or microfluidic device with the crystal orientation line enables high-precision production with improved reproducibility and reduced number of defective products.

[0029] Thus, in a preferred embodiment of the present 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.

[0030] The single-crystalline wafer is preferably a single-crystalline wafer obtained by cutting a single crystal from a Czochralski process. In certain embodiments, the single-crystalline wafer is a single crystal obtained from a material that crystallizes within a diamond or perovskite crystal structure. Suitable materials are known to those skilled in the art and include, but are not limited to, single-crystalline silicon, single-crystalline germanium, or single-crystalline gallium arsenide. In a preferred embodiment, the single-crystalline material is single-crystalline silicon.

[0031] For optimal cleavage properties, the wafer is cut from a single crystal obtained by the Czochralski process and cut along the

[0100] crystal orientation. As shown in Figure 2, the wafer cut from a single crystal with the

[0100] orientation exhibits ideal cleavage behavior along the crystal orientation lines.

[0032] Corresponding single-crystalline wafers are commercially available, for example, from Samsung, KR or Micron, USA.

[0033] Often, suitable single-crystalline wafers are circular and have one or two flat surfaces. As outlined in Figure 4, the flat surface (7) of the wafer (6) corresponds to the crystal orientation lines of the wafer. All further corresponding crystal orientation lines are perpendicular or parallel to the flat surface of the wafer.

[0034] Thus, in a preferred embodiment of the present invention, the single-crystalline wafer is a wafer with the

[0100] crystal orientation, and the front end of the microfluidic device is aligned with or corresponds to the

[0010] or

[0001] crystal orientation lines. In a preferred embodiment, the wafer is a circular wafer with a flat surface corresponding to the crystal orientation lines. In some embodiments, the wafer includes a depression indicating a crystal orientation line that can function as a predetermined breaking point.

[0035] In some embodiments of the present invention, the wafer substrate in step a) of the method of the present invention is a wafer substrate cut from a single crystal with the

[0100] crystal orientation, and the wafer substrate comprises a flat surface corresponding to the crystal orientation lines.

[0036] The wafer may be thick or thin as necessary. In a preferred embodiment, the thickness of the wafer is about 2 mm or less, for example, about 125 μm to about 2 mm. In some embodiments, the single crystal wafer is less than 1.5 mm thick and, for example, has a thickness of about 250 μm to 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, for example, about 300 μm to about 750 μm.

[0037] The microfluidic device may be fabricated on the wafer by any suitable means. Those skilled in the art recognize suitable means for fabricating a microfluidic device on a single crystal wafer. The method may include chemical or mechanical methods. In some embodiments, the microfluidic device is fabricated by etching the microfluidic device into the single crystal wafer. In some embodiments, the microfluidic device is fabricated by laser etching or laser ablation. In different embodiments, the microfluidic device is fabricated by sandblasting. In some embodiments, the microfluidic device is fabricated by micro lithography. In some embodiments, the microfluidic device is fabricated by a combination of different methods, such as a combination of etching and laser ablation.

[0038] Separate from 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, provided that at least one side, i.e., the front end, is aligned with the crystal orientation line.

[0039] In a preferred embodiment, the microfluidic device is rectangular and has 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 or corresponds to a further crystal orientation line perpendicular to the rear end crystal orientation line. In such an embodiment, the method preferably fabricating at least one microfluidic device having at least two microfluidic structures on the single crystal wafer, the microfluidic structures being aligned along a crystal orientation, the front and rear ends of the device being parallel, each being aligned and corresponding to a crystal orientation line, and optionally, the side ends being perpendicular to the front and rear ends, each being aligned and corresponding to a crystal orientation line perpendicular to the crystal orientation lines of the front and rear ends.

[0040] The method is also suitable for mass production of high-precision microfluidic devices. Thus, the method may include fabricating a plurality of microfluidic devices on a single single crystal wafer. The microfluidic devices may or may not be identical. Preferably, the single crystal wafer comprises a plurality of identical microfluidic devices aligned in parallel, and their respective rear and side ends are aligned with crystal orientation lines to enable easy separation. See, for example, FIG. 4.

[0041] Thus, 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, and the method a) providing a wafer substrate of single crystal material; b) fabricating a plurality of microfluidic devices on the wafer substrate, each comprising at least two microfluidic structures, each of said structures being located at the front end of a corresponding microfluidic device, and the microfluidic structures of each device being aligned with a crystal orientation line; c) separating the microfluidic device (1) from the substrate by cleaving the wafer along the crystal orientation line; and including.

[0042] In a preferred embodiment, the wafer substrate in step a) of the method of the present invention is a wafer substrate cut from a single crystal material with a

[0100] crystal orientation, and the wafer substrate has a flat surface corresponding to the crystal orientation line.

[0043] 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.

[0044] Therefore, in some embodiments of the present invention, the wafer substrate is the wafer substrate defined above, and step b) of the method includes 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 the front end of the respective microfluidic device, the microfluidic structures being aligned with the crystal orientation line, and at least one front end of the plurality of microfluidic devices being aligned with or preferably corresponding to the flat surface of the single crystal wafer substrate.

[0045] The method of the present invention is particularly suitable for mass production of rectangular microfluidic devices. Therefore, in some embodiments, the present invention relates to a method as defined above for producing a plurality of microfluidic devices, wherein the microfluidic device comprises 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.

[0046] Therefore, 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, 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 comprises a) providing a wafer substrate of single crystal material; b) fabricating a plurality of microfluidic devices on the wafer substrate, each comprising at least two microfluidic structures, each of said structures being located at the front end of a respective microfluidic device, the microfluidic structures being aligned along a crystal orientation line, the plurality of microfluidic devices being fabricated in a checkerboard pattern, the microfluidic devices being positioned parallel to each other such that a first row of microfluidic devices has a front end aligned with the crystal orientation line, parallel rear ends aligned with different parallel crystal orientation lines, and side ends aligned with perpendicular crystal orientation lines, a side end of one microfluidic device being adjacent to a side end of a further microfluidic device, and a rear end of a microfluidic device being adjacent to a front end of a microfluidic device; c) separating the microfluidic devices (1) from the substrate and from each other by cleaving the wafer along the crystal orientation line; comprising.

[0047] The microfluidic devices may be the same or different microfluidic devices. Preferably, the microfluidic devices are the same.

[0048] The microfluidic device or devices may be cleaved from the wafer by any suitable method. Those skilled in the art will recognize suitable methods of cleaving a wafer along a crystal orientation line. Suitable methods include cutting and breaking or combinations thereof. In a preferred embodiment, the cleavage comprises breaking the microfluidic devices from the microfluidic wafer along the crystal orientation line. The breaking may be done manually or using a machine. To improve the accuracy of cleavage of a single crystal wafer, the wafer may be covered with a plate containing a predetermined break point or break line adapted to the wafer, the break point or break line being adapted to the crystal orientation line of the single crystal wafer. In such an embodiment, the plate having the predetermined break point or break line is cleaved and in particular broken together with the single crystal wafer.

[0049] In some embodiments, the wafer may include a predetermined breaking line or breaking point. The wafer may be slightly chipped or indented at a predetermined portion to form a predetermined breaking point. It is also possible to add a predetermined breaking point during the process of fabricating the microfluidic device on the wafer. For example, the predetermined breaking point or breaking line may be etched on the wafer. Such a predetermined breaking point or breaking line may be fabricated in the same manner as the microfluidic device, for example, by etching, particularly laser etching, laser ablation, sandblasting or microlithography.

[0050] In some embodiments, the microfluidic device is covered with a closure device before or after cleavage. 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.

[0051] The closure device may be permanently attached to the microfluidic device, for example, by using an adhesive or atomic bonding. In some embodiments, the closure device is placed on the microfluidic device and held in place by a separate holding structure.

[0052] In a preferred embodiment, the closure device covers the single crystal wafer and includes a predetermined cleavage site (5) aligned with the crystal orientation line of the wafer. In this case, the predetermined cleavage site of the closure device may be suitable for cleaving the closure device and the microfluidic device of the wafer. See FIG. 5.

[0053] The method of the present invention is particularly suitable for the production of microfluidic nozzles, preferably nozzles for use in inhalation devices, particularly impinging nozzles. An exemplary impinging nozzle is shown in FIG. 3.

[0054] In a collision-type 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 that intersect each other at a collision point. The collision of the two fluid flows at the collision point generates a respiratory aerosol.

[0055] To provide an ideal respiratory aerosol, the ejection trajectories and distances of the outlet channels must be precisely defined. When the nozzle is produced according to the method of the present invention and the ejection channels are aligned with the crystal orientation lines, the number of nozzles that cannot be used due to inaccurate cutting or sawing is reduced, so that the amount of defective nozzles can be reduced.

[0056] Accordingly, in a particular embodiment, the present invention is a method for producing a microfluidic device as defined above, wherein the microfluidic device is a nozzle for an inhalation device for spraying a liquid into a respiratory aerosol, the nozzle body (1) has a front end portion (1B), at least two microfluidic structures are ejection channels (2, 2'), each channel (2, 2') has a channel outlet (2A, 2A'), and the ejection channels (2, 2') are arranged to eject the liquid along respective ejection trajectories that intersect each other at a collision point. The nozzle body (1) has a flat surface (1A), at least two liquid channels (2, 2') are fixed on the flat surface (1A) at a defined depth (D), and in a view perpendicular to the longitudinal axis (X) of the nozzle body (1), it has a front end portion (4B) that coincides with the front end portion (1B) of the nozzle body (1). The nozzle body is made at least partially from a single-crystal material, and the channel outlet of each ejection channel is positioned in line with the crystal orientation such that the collision point is on the longitudinal axis (X) of the nozzle body. The method comprises a) Preparing a nozzle body (1) having a front end portion (1B) and comprising at least two ejection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), the ejection channels (2, 2') being arranged to eject liquid along respective ejection trajectories that intersect each other at a collision point on the longitudinal axis (X), the nozzle body (1) having a flat surface (1A), at least two liquid channels (2, 2') being fixed on the flat surface (1A) at a defined depth (D), the following steps: (i) Providing a wafer substrate of single crystal material, (ii) Fabricating a nozzle body comprising at least two liquid channels (2, 2') on one surface (1A) of the substrate, the channels (2, 2') having a defined depth (D), the liquid channel outlets being aligned along the crystal orientation, (iii) Separating the body (1) from the substrate by cleaving the wafer along the crystal orientation line, including, b) Optionally, covering the nozzle body (1) with a closing device (3), relating to a method.

[0057] In some embodiments of the invention, the channel outlets are fabricated on the crystal orientation line and fabricated to eject liquid along respective ejection trajectories that intersect each other at a collision point on the longitudinal axis (X). Preferably, the channel outlets are each equidistant from the longitudinal axis.

[0058] In particular, the method is suitable for producing a plurality of microfluidic nozzles as defined above.

[0059] In a preferred embodiment, the nozzle is covered by a closing device, preferably a lid. In some embodiments, the closing device is a cover. The closing device may be of the same or a different material as the nozzle. In some embodiments, the closing device is of a different material. In a particular embodiment, the closing device is made of glass.

[0060] In some embodiments, the single crystal wafer is covered with a lid wafer, and the wafer is cleaved together with the lid wafer. In a preferred embodiment, the cleaved lid wafer is retained on the cleaved nozzle to obtain a nozzle covered with a closure device. In some embodiments, the lid wafer includes a crystal orientation line of the single crystal wafer and a predetermined breaking point aligned with the nozzle fabricated thereon.

[0061] The nozzles produced by the method of the present invention exhibit a higher degree of accuracy and aerosol quality reproducibility.

[0062] Generally, the microfluidic device produced by the method according to the present invention can reduce the extra space required as a safety measure to address inaccuracies, thus reducing the overall amount of material required. Generally, in this method, the number of defective microfluidic devices can be reduced.

[0063] 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 microfluidic device comprises at least two microfluidic structures, each of said structures being located at the front end of the microfluidic device, and the front end of the microfluidic device and the microfluidic structures being aligned with a crystal orientation line. An example of such a wafer is shown in FIG. 4.

[0064] The single crystal wafer comprising a plurality of microfluidic devices is preferably a wafer substrate cut from a single crystal of the

[0100] crystal orientation, and the wafer substrate comprises a flat surface corresponding to the crystal orientation line.

[0065] A single-crystal wafer comprising a plurality of microfluidic devices according to this aspect of the present invention is preferably a single-crystal wafer obtained by cutting a single crystal from a Czochralski process. In particular, a single-crystal wafer comprising a plurality of microfluidic devices is a single crystal obtained from a material that crystallizes within a diamond or perovskite crystal structure. Suitable materials are known to those skilled in the art 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.

[0066] In a preferred embodiment, the plurality of microfluidic devices are arranged in a parallel orientation. The plurality of microfluidic devices can be fabricated on the wafer by any suitable means as described above. Suitable means include, but are not limited to, etching, laser etching, laser ablation, sandblasting, and microlithography.

[0067] In a particular embodiment, the microfluidic device provided on the single-crystal wafer comprises a front end, a rear end, and two side ends, and the device is aligned such 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 a crystal orientation line perpendicular to the first and second crystal orientation lines so that the microfluidic device can be separated by cutting or breaking along the crystal orientation lines.

[0068] In a particular embodiment, the plurality of microfluidic devices provided on the single-crystal wafer are arranged in a checkerboard pattern, and the rear end of one device is in contact with the front end and the side ends of another device. Thus, the wafer enables the plurality of microfluidic devices to be obtained by cleaving the devices along their respective crystal orientation lines. In particular, the microfluidic devices are obtained by breaking the devices along their respective crystal orientation lines.

[0069] Accordingly, in a further aspect, the present invention relates to a microfluidic device obtainable by the above method. In particular, the present invention relates to a microfluidic nozzle obtainable by the method defined above.

[0070] Accordingly, in one aspect, the present invention is a microfluidic device comprising at least two microfluidic structures, each of said structures being located at the front end of the microfluidic device, the microfluidic device being at least partially made from a single crystal material, and the front end of the microfluidic device and said microfluidic structures being aligned with the crystal orientation line of the single crystal material. Preferably, the front end of the device is on the crystal orientation line.

[0071] In particular, the front end of the microfluidic device follows or corresponds to the crystal orientation line of the single crystal material. Most preferably, the front end of the microfluidic device is obtained by cleaving the device from a single crystal wafer along the crystal orientation line.

[0072] 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 in the

[0100] crystal orientation, and the crystal orientation line along which the front end of the microfluidic device is aligned corresponds to the

[0010] or

[0001] crystal orientation line.

[0073] Aligning the microfluidic structures with the crystal orientation line enables a simple and straightforward method of obtaining a reproducible microfluidic device. 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 specific structures such as microfluidic filter structures. The microfluidic structure also includes microfluidic structures that can comprise additional components that are not part of the single crystal wafer substrate, such as microfluidic valves or mixing chambers.

[0074] Particularly, a microfluidic structure comprising a microfluidic channel having a microfluidic channel outlet is preferred. Alignment along the crystal orientation line enables precise positioning, and when the device is cleaved along the crystal orientation line, the precise positioning is not affected by, for example, imprecise cutting or sawing. Preferably, the microfluidic structure is present in a single crystal material and is, for example, etched.

[0075] Those skilled in the art recognize suitable single crystal materials. Preferably, the single crystal material is a material that crystallizes in a diamond crystal structure or a perovskite crystal structure. Materials preferred for the microfluidic device include single crystal silicon, single crystal germanium, or single crystal gallium arsenide. In a preferred embodiment, the single crystal material is single crystal silicon.

[0076] The microfluidic device according to the present invention preferably comprises a front end portion and a rear end portion. The microfluidic device further comprises two or more side end portions, but it is preferred that the device comprises two side end portions and is generally rectangular in shape. However, the microfluidic device is not limited to a rectangular shape.

[0077] The single crystal material enables a small and compact microfluidic device with a thin thickness. In some embodiments, the microfluidic device according to the present invention has a thickness of about 1.5 mm or less. In a preferred embodiment, the microfluidic device is less than 1.5 mm thick and has, for example, 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 about 300 μm to about 750 μm.

[0078] At least two microfluidic structures preferably comprise a microfluidic channel with a microfluidic channel outlet. The channel outlet can be positioned with high precision to ensure compatibility with other devices, for example, to transfer fluid from one device to another. The microfluidic device according to the present invention exhibits high precision compared to microfluidic devices obtained by cutting or sawing, thus reducing the number of non - conforming devices due to misaligned cutting or sawing.

[0079] 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 is aligned with the crystal orientation line.

[0080] The microfluidic device can be of any type of microfluidic device. In some embodiments, the microfluidic device is an open - type microfluidic device. In some embodiments, the microfluidic device is at least partially closed. In some embodiments, the microfluidic device comprises a closing device that covers at least a part of the device. In some embodiments, the device comprises a closing device that covers the microfluidic structure. In some embodiments, the microfluidic device comprises a closing device that covers part or the whole of the device. The closing device may be a lid. In some embodiments, the closing device is a cover.

[0081] When the device comprises a closing device, the closing device can be made of any material. In some embodiments, the closing device is made of the same single - crystal material. In some embodiments, the closing device is made of different materials. Any material suitable for use in microfluidic applications can be used. Suitable materials are known to those skilled in the art. In some embodiments where the microfluidic device comprises a closing device, the closing is made of glass.

[0082] The microfluidic device according to the present invention can be any microfluidic device that requires a high degree of accuracy. In a preferred embodiment of the present invention, the microfluidic device is for an inhalation device. In some embodiments, the microfluidic device is a valve, or includes a valve, or is part of a valve. In other embodiments, the microfluidic device is a filter unit, or includes a filter unit. In some embodiments, the microfluidic device according to the present invention is a nozzle for an inhalation device. In a particular embodiment, the microfluidic device according to the present invention is an impact nozzle.

[0083] Accordingly, in a particular embodiment, the present invention provides a microfluidic nozzle, wherein the nozzle is a nozzle for an inhalation device for spraying a liquid into a respiratory aerosol, the nozzle body (1) has a front end portion (1B), at least two microfluidic structures are ejection channels (2, 2'), each channel (2, 2') has a channel outlet (2A, 2A'), and the ejection channels (2, 2') are arranged to eject liquid along respective ejection trajectories that intersect each other at a collision point. The nozzle body (1) has a flat surface (1A), at least two liquid channels (2, 2') are fixed on the flat surface (1A) with a defined depth (D), and when viewed perpendicular to the longitudinal axis (X) of the nozzle body (1), it has a front end portion (4B) that coincides with the front end portion (1B) of the nozzle body (1). The present invention relates to a microfluidic nozzle, characterized in that the nozzle body is made of a single crystal material, and the channel outlet of each ejection channel is positioned in a straight line with the crystal orientation such that the collision point is on the longitudinal axis of the nozzle body.

[0084] In a preferred embodiment of the present invention, the microfluidic channel outlet of the ejection channel is on the crystal orientation line of the single crystal material.

[0085] The single-crystal material of the nozzle preferably corresponds to a single-crystal material obtained from a single crystal sliced along one crystal plane. More preferably, the single-crystal material is a single-crystal material obtained from a single crystal sliced in the

[0100] crystal orientation, and the crystal orientation line along which the front end portion of the microfluidic device is aligned corresponds to the

[0010] or

[0001] crystal orientation line.

[0086] In some embodiments, the nozzle comprises a closing device, preferably a lid. In some embodiments, the closing device is a cover. The closing device may be made of the same material as the nozzle or a different material. In some embodiments, the closing device is made of glass.

[0087] The present invention further relates to the use of a microfluidic device obtained by the method defined above as a nozzle in an inhalation device for spraying a liquid into a respiratory aerosol.

[0088] In a particular aspect, the present invention further relates to an inhalation device for spraying a liquid into a respiratory aerosol, comprising at least one microfluidic device as defined above, in particular a nozzle as defined above.

[0089] All embodiments described above in connection with the method of the present invention apply to all aspects of the present invention, including the microfluidic device according to the present invention and the single-crystal wafer according to the present invention.

[0090] The present invention further relates to the following numbered items. 1. A microfluidic device comprising at least two microfluidic structures, each of said structures being located at the front end portion of the microfluidic device, the microfluidic device being at least partially made of a single-crystal material, and the front end portion of the microfluidic device and the microfluidic structures being aligned with a crystal orientation line of the single-crystal material. 2. The microfluidic device according to item 1, wherein the microfluidic structure is a microfluidic channel comprising a microfluidic channel outlet. 3. The microfluidic channel outlet is located at the front end of the microfluidic device and is aligned with the crystal orientation line. The microfluidic device according to item 2. 4. The microfluidic device is made of a single crystal material, and the material crystallizes in a diamond cubic crystal structure or a perovskite crystal structure. The microfluidic device according to any one of items 1 to 3. 5. The single crystal material is selected from silicon, germanium, and gallium arsenide. The microfluidic device according to any one of items 1 to 4. 6. The microfluidic structure exists in the single crystal material. The microfluidic device according to any one of items 1 to 5. 7. The microfluidic device includes a closing device. The microfluidic device according to any one of items 1 to 6. 8. The closing device is made of the same single crystal material. The microfluidic device according to item 7. 9. The closing device is made of different materials. The microfluidic device according to item 7. 10. The closing device is made of glass. The microfluidic device according to item 9. 11. The microfluidic device is a nozzle. The microfluidic device according to any one of items 1 to 10. 12. The nozzle is a collision type nozzle. The microfluidic device according to item 11. 13. The nozzle is a nozzle for an inhalation device for spraying a liquid into a respiratory aerosol. The nozzle body (1) has a front end portion (1B), and at least two microfluidic structures are ejection channels (2, 2’). Each channel (2, 2’) has a channel outlet (2A, 2A’). The ejection channels (2, 2’) are arranged to eject the liquid along respective ejection trajectories that intersect at a collision point. The nozzle body (1) has a flat surface (1A), and at least two liquid channels (2, 2’) are on the flat surface (1A). In a view perpendicular to the longitudinal axis (X) of the nozzle body (1), it has a front end portion (3B) that coincides with the front end portion (1B) of the nozzle body (1). The nozzle body is made of a single crystal material, and the channel outlets of each ejection channel are positioned in alignment with the crystal orientation such that the collision point is on the longitudinal axis of the nozzle body. The microfluidic device according to item 12. 14. The microfluidic device according to item 13, wherein the nozzle comprises a closing device. 15. A single crystal wafer comprising a plurality of microfluidic devices according to any one of items 1 to 14. 16. The single crystal wafer according to item 15, wherein the plurality of microfluidic devices are arranged in a parallel orientation. 17. The microfluidic device comprises a front end portion, a rear end portion, and two side end portions. The front end portion of the device is aligned with a first crystal orientation line, the rear end portion is aligned with a second crystal orientation line parallel to the first crystal orientation line, and the side end portions are aligned with crystal orientation lines perpendicular to the first and second crystal orientation lines such that the device can be separated by cutting or breaking the microfluidic device along the crystal orientation line. The single crystal wafer according to item 16. 18. The single crystal wafer according to item 17, wherein the plurality of microfluidic devices are arranged in a checkerboard pattern, the rear end portion of one device is in contact with the front end portion of another device, and the side end portion of one device is in contact with the side end portion of another device. 19. A method for producing a microfluidic device according to any one of items 1 to 14, a) providing a wafer substrate of a single crystal material; b) fabricating at least one microfluidic device having at least two microfluidic structures on the wafer substrate, the microfluidic structures being aligned along a crystal orientation; c) separating the microfluidic device (1) from the substrate by cleaving the wafer along a crystal orientation line; comprising. 20. A method for producing a microfluidic device according to item 19, comprising etching the microfluidic structure of the device onto the wafer. 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, and the method comprises: a) preparing a nozzle body (1) having a front end portion (1B) and comprising at least two ejection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), the ejection channels (2, 2') being arranged to eject liquid along respective ejection trajectories that intersect each other at a collision point, at least one recess (3) being provided in the front end portion (1B) where at least two of the channel outlets (2A, 2A') are positioned, the nozzle body (1) having a flat surface (1A), at least two liquid channels (2, 2') being fixed on the flat surface (1A) at a defined depth (D), the following steps: (i) providing a wafer substrate of single crystal material, (ii) fabricating at least two liquid channels (2, 2') on one surface (1A) of the substrate, the channels (2, 2') having a defined depth (D), the liquid channel outlets being aligned along a crystal orientation, (iii) separating the body (1) from the substrate by cleaving the wafer along a crystal orientation line, including; b) optionally, covering the nozzle body (1) with a closure device, including. 22. A nozzle for an inhalation device obtainable by the method according to item 21. 23. Use of a microfluidic device according to any one of items 12 to 14 as a nozzle in an inhalation device for spraying a liquid into a respiratory aerosol. 24. An inhalation device for spraying a liquid into a respiratory aerosol, comprising at least one microfluidic device according to any one of items 1 to 14.

Description of the reference numerals

[0091] 1 Nozzle body 1A Flat surface 1B Front end portion 2,2’ ejection channel, liquid channel, channel 2A,2A’ channel outlet 2B,2B’ front-end channel outlet 3 closing device 4 separation line 4’ optimal separation line 5 predetermined splitting site 6. single crystal wafer 7. flat surface of the wafer A,A’ injection axis X longitudinal axis Y,Y’ lateral distance D depth

Claims

1. A microfluidic device comprising at least two microfluidic structures, each of said structures being located at the front end of said microfluidic device, said microfluidic device being at least partially made of a single crystal material, the front end of said microfluidic device and said microfluidic structures being aligned with the crystal orientation line of said single crystal material, and said microfluidic device being a nozzle for an inhalation device.

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

3. The microfluidic device according to claim 1 or 2, wherein said microfluidic device is made of a single crystal material, and said material crystallizes in a diamond cubic structure or a perovskite crystal structure.

4. The microfluidic device according to any one of claims 1 to 3, wherein said microfluidic device is made of a single crystal material, and said 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 said microfluidic device comprises a closing device.

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

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

8. The nozzle is a nozzle for an inhalation device for spraying a liquid into a respiratory aerosol, the nozzle body (1) has a front end portion (1B), said at least two microfluidic structures are ejection channels (2, 2'), each channel (2, 2') has a channel outlet (2A, 2A'), and said ejection channels (2, 2') are arranged to eject a liquid along respective ejection trajectories that intersect each other at an impact point. The nozzle body (1) has a flat surface (1A), said at least two liquid channels (2, 2') are on said flat surface (1A), and when viewed perpendicular to the longitudinal axis (X) of said nozzle body (1), it has a front end portion (4B) that coincides with the front end portion (1B) of said nozzle body (1). The nozzle body is made of a single crystal material having a crystal orientation line, and the channel outlets of the respective ejection channels are positioned in a straight line with the crystal orientation so that the collision point is on the longitudinal axis of the nozzle body. The microfluidic device according to claim 7.

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

10. The wafer is - a first crystal orientation line, - a second crystal orientation line parallel to the first crystal orientation line, - a plurality of crystal orientation lines perpendicular to the first and second crystal orientation lines, and The microfluidic device is - a front end portion, - a rear end portion, - two side end portions, and The device is aligned such that the front end portion of the device is aligned with the first crystal orientation line of the wafer, the rear end portion is aligned with the second crystal orientation line of the wafer, and the side end portions are aligned with the crystal orientation lines of the wafer perpendicular to the first and second crystal orientations. The single crystal wafer according to claim 9.

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

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 a) preparing a nozzle body (1) having a front end portion (1B) and comprising at least two ejection channels (2, 2'), each channel (2, 2') having a channel outlet (2A, 2A'), the ejection channels (2, 2') being arranged to eject liquid along respective ejection trajectories that intersect each other at a collision point, at least one recess (3) being provided in the front end portion (1B) in which at least two of the channel outlets (2A, 2A') are positioned, the nozzle body (1) having a flat surface (1A), the at least two liquid channels (2, 2') being fixed on the flat surface (1A) at a defined depth (D), the following steps: (i) providing a wafer substrate of a single crystal material having a crystal orientation line, Step (ii) of fabricating at least two liquid channels (2, 2') on one surface (1A) of the substrate, wherein the channels (2, 2') have a defined depth (D), and the outlets of the liquid channels are aligned along the crystal orientation line. Step (iii) of separating the body (1) from the wafer substrate by cleaving the wafer along the crystal orientation line. Steps, including: b) Optionally, covering the nozzle body (1) with a closure device. A method, including:

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 the microfluidic device according to any one of claims 6 - 8 as a nozzle in an inhaler for spraying a liquid, preferably a medically active liquid, into a respiratory aerosol.

15. An inhaler for spraying a liquid into a respiratory aerosol, comprising at least one microfluidic device according to any one of claims 1 - 8.

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