METHOD AND SYSTEM FOR THE MANUFACTURING OF MICROSTRUCTURES

Description

[0001] The invention relates to a method for producing microstructures, in particular a method for producing microarrays. Furthermore, the invention relates to a system for producing microstructures, in particular a system for producing microarrays.

[0002] Microarrays consist of numerous microneedles, typically arranged in or connected to a carrier element such as a patch, adhesive bandage, or similar product. The length of the microneedles is specifically designed so that, when inserted into a patient's skin, they penetrate only to a depth that minimizes contact between the needle tips and nerves or blood vessels. The needles contain an active ingredient, such as a medication. This active ingredient may be applied to the top of the needle or contained within the needles themselves. When the active ingredient is contained within the needles, the needles or their components are made of a material that dissolves in the patient's skin.

[0003] Microarrays are manufactured, for example, using silicone molds with numerous openings. A liquid containing the active ingredient is typically applied to the top of the silicone mold to fill these openings. After the liquid has dried, another liquid may be applied. The carrier element is then applied to the underside of the material embedded in the silicone mold. The microneedles are removed from the silicone mold and subsequently packaged.

[0004] The production of microarrays is currently very complex and expensive.

[0005] Furthermore, problems arise when filling the mold openings, which are usually conical or pyramidal. Often, the mold openings are not sufficiently filled with filler material. For example, cavities and / or air pockets can occur. This problem is particularly common at the tips of the mold openings, especially the conical or pyramidal ones. Such faulty filling can lead to application problems, for example, because the faulty tips may not penetrate the skin properly, and / or the lack of formulation in the cavities can result in insufficient drug dosage.

[0006] Impurities and / or contamination cause further problems in today's microarray manufacturing.

[0007] The prior art relating to the present application is described in EP 2 343 101 A1, US 2020 / 197679 A1, EP 3 144 030 A1, US 2017 / 050010 A1, US 2019 / 030309 A1, and KR 2017 0011578 A.

[0008] The object of the invention is to provide a method for the production of microstructures, in particular microarrays, wherein the scalability is improved and which is preferably suitable for the production of high volumes. Furthermore, it is an object of the invention to provide a corresponding system for the production of microstructures.

[0009] According to the invention, the problem is solved by a method according to claim 1 or a system according to claim 14.

[0010] The inventive method for producing microstructures is, in particular, a method for producing microarrays. One, preferably first, step of the method consists of providing a preferably planar mold element. The mold element has at least one, preferably several, mold openings for the microstructures to be produced. The at least one mold opening is, in particular, a negative mold for the microstructures to be produced. The mold opening corresponds, in particular, to a cavity. The at least one mold opening has a first opening and a second opening, in particular opposite the first opening. It is therefore preferred that the mold opening is open on both sides. It is preferred that the first opening and the second opening open the mold opening towards the surroundings.Preferably, a fluid connection between the mold opening and the environment is formed through the first and second openings. The mold opening preferably extends from one side of the planar mold element to a side of the mold element opposite the first side. If, in a preferred embodiment, the mold element is designed as a film, the mold opening extends, in particular, from one side of the film to the other. It is preferred that the at least one mold opening is an embossed mold opening, preferably produced by means of an embossing roller. A further step of the process consists of providing a first formulation at the second opening. It is preferred that the first formulation comprises at least one active ingredient. The first formulation is particularly designed to form the tips of the microstructures.The first formulation is provided in such a way that it is in contact with the second opening. It is particularly preferred that the formulation is provided in such a way that the second opening is immersed in the first formulation. A further step of the process consists of generating a negative pressure and / or suction in the mold opening. The negative pressure can also be described as a vacuum, preferably not a complete one. Negative pressure here refers in particular to a negative pressure ratio compared to the ambient pressure. A further, and in particular the next, step of the process consists of drawing the first formulation into the mold opening through the second opening. This drawing in occurs at least partially due to the negative pressure in the mold opening. It is preferred that the first formulation is drawn in through the second opening.In addition to the intake of the first formulation by means of negative pressure, it is preferred that intake of the first formulation into the mold opening also occurs by capillary action. It is preferred that this intake by capillary action takes place before and / or during intake by means of negative pressure. The intake of the first formulation into the mold opening is particularly necessary for the formation of a portion of the microstructures to be produced. This intake is specifically achieved by drawing the formulation in or sucking it in.

[0011] In a preferred embodiment, the vacuum is generated in the mold opening by expanding the volume of the mold opening. The volume to be expanded is, in particular, the volume between the first and second openings of the mold. It is preferred that the expansion of the mold opening volume is such that the resulting volume increase essentially corresponds to the volume of the first formulation to be received. In particular, the expansion of the mold opening volume is at least 3%, preferably at least 5%, and most preferably at least 10%, with a further preference being an expansion of the mold opening volume of at least 20%.

[0012] A further step of the process consists of reducing the volume of the mold opening, wherein this step is carried out before generating the vacuum in the mold opening, and in particular before expanding the volume of the mold opening. The step of providing the first formulation preferably takes place before and / or after reducing the volume. It is preferred that the reduction of the mold opening volume is carried out such that the resulting volume reduction essentially corresponds to the volume of the first formulation to be received. In particular, the volume of the mold opening is reduced by at least 3%, preferably by at least 5%, and most preferably by at least 10%, with a further preference being a reduction of at least 20%.

[0013] The volume of the mold opening is reduced by at least partially compressing the mold element. Compression is achieved in particular by pressing and / or longitudinal stretching. For compression, it is preferred that the mold element is pressed on the side of the first opening, preferably on both sides of the two openings, and / or that the mold element is stretched, particularly in the longitudinal direction.

[0014] It is preferred that the compression of the forming element is carried out by means of at least one roller. The roller is, in particular, a press roller. The at least one press roller presses on at least one surface, especially on the surface of the first opening of the forming element. Compression is particularly preferably carried out by means of two rollers on both sides of the forming element. It is preferred that the two rollers are arranged offset in the rolling direction.

[0015] Preferably, a further step of the method consists of arranging an auxiliary element on the side of the mold element having the first opening. The auxiliary element is brought into contact with this side, and preferably bonded to it adhesively. The auxiliary element preferably comprises an auxiliary film, and in particular consists of one. The auxiliary element is preferably arranged before the creation of the vacuum in the mold opening, and especially preferably before the expansion of the mold opening's volume. In particular, the auxiliary element is arranged before or during the reduction of the mold opening's volume.

[0016] Preferably, a further step of the method consists of closing the first opening of the mold cavity. In particular, the first opening is closed in a substantially airtight manner. It is preferred that the closing is carried out with the auxiliary element, so that the auxiliary element seals the first opening of the mold cavity. The closing step of the first opening takes place before the negative pressure is created in the mold cavity. In particular, the closing of the first opening takes place after reducing the volume of the mold cavity, preferably after compressing the mold element.

[0017] A preferred further step of the process consists of removing the auxiliary element, preferably from the mold element. This removal takes place after the first formulation has been received in the mold opening. It is preferred that the removal is carried out by pulling off the auxiliary element.

[0018] It is preferred that the at least one mold opening is cylindrical or conical. The cylindrical or conical shape has, in particular, a round, triangular, or rectangular, and especially preferably, a square cross-section. It is preferred that the conical shape tapers from the first opening to the second opening of the mold. It is possible that the conical shape is designed as a truncated cone. A conical shape with a rectangular cross-section can also be described as a pyramid shape.

[0019] The second opening preferably has a smaller cross-sectional area than the first opening. Preferably, the cross-section of the mold opening tapers from the first opening towards the second opening.

[0020] Preferably, the reduction of the mold opening volume, and in particular the at least partial compression of the mold element, is achieved by bending the mold element. The bending is preferably performed along a transverse direction of the mold element, such that a bending edge is perpendicular to the longitudinal direction of the mold element. Particularly preferably, the bending is performed in the direction of the first opening and / or in a direction opposite to the direction of the narrowing of the mold opening, especially in the case of a conical mold opening. Thus, a compressed fiber of the mold element is preferably located on the side of the first opening and / or on the side where the mold opening is enlarged. The bending is preferably performed at an angle of 0° to 180°, preferably from 10° to 90°, and most preferably from 30° to 60°.Due to bending, the molded element has, in particular, a neutral fiber and a compressed fiber on the side of the molded element where the bending occurs, as well as a straight fiber on the side opposite the compressed fiber. Preferably, a compressed area is present on the side of the compressed fiber of the molded element, and a straight area is present on the side of the straight fiber of the molded element. Bending preferably causes the compressed area, and in particular the compressed fiber, of the molded element to decrease in size. Thus, the mold opening, and preferably the volume of the mold opening, in this area of ​​the molded element also decreases. Likewise, bending preferably causes the straight area, and in particular the straight fiber, of the molded element to increase in size. Thus, the mold opening, and preferably the volume of the mold opening, in this area of ​​the molded element also increases in size.In a preferred embodiment, particularly in a conical mold opening, the mold opening has a significantly larger volume on the side with the compressed fiber than on the side with the stretched fiber. Bending thus preferably results in a greater reduction in volume on the side with the compressed fiber than in an increase in volume on the side with the stretched fiber. Overall, bending therefore preferably results in a reduction in the total volume of the mold opening.

[0021] The bending is preferably carried out with the at least one roller. The at least one roller is then preferably a bending roller.

[0022] The volume is increased in particular by returning the mold element to its original shape. This return is preferably achieved by bending back the mold element after bending and / or by relaxing the compressed, in particular pressed and / or longitudinally stretched, mold element.

[0023] It is preferred that the molded element has a film, and in particular consists of one.

[0024] It is particularly preferred that the molded element is made of TPU, PC or PETG, or in particular consists of these materials.

[0025] The molded element is preferably compressible. It is preferred that the molded element be elastic.

[0026] After the first formulation is drawn into the mold, a second formulation is preferably supplied to the first opening. It is preferred that the second formulation is free of active ingredients. However, it is also possible that the second formulation contains at least one active ingredient. After the second formulation is supplied, it is drawn into the mold opening through the first opening. Preferably, the mold opening, and in particular the remaining volume of the mold opening, is completely filled with the second formulation. The second formulation combines with the first formulation, preferably by a metallurgical bond. The second formulation is preferably drawn in by pressing, in particular by injection. Preferably, this pressing is carried out using a roller.It is preferred that, during the pickup step, the formulation is in contact with the first opening on one side and covered on the other side by a formulation element, in particular the second formulation element described below. Preferably, the pressure for pressing in the second formulation, in particular the roller, is applied to this formulation element.

[0027] Preferably, the first formulation is provided by means of a first formulation element. The first formulation element preferably comprises a film, and in particular consists of one. The first formulation element contains the first formulation. Preferably, the first formulation is arranged on the first formulation element, particularly in droplet form. It is preferred that the first formulation element has a formulation receptacle, preferably a recess. In other words, this formulation receptacle is a kind of cup-shaped form in the formulation element in which the formulation is located. Alternatively or additionally, the second formulation is provided by means of a second formulation element, which contains the second formulation.The second formulation element is specifically designed with one or more features of the first formulation element.

[0028] After the first formulation and / or the second formulation is taken into the mold, drying is carried out. This drying is performed, in particular, through the first opening of the mold. The drying is carried out, preferably, by means of a warm airflow, which is in direct contact with the first and / or second formulation. It is preferred that the drying process causes the first and / or second formulation to solidify into microstructures. In addition to or as an alternative to the airflow, drying can be carried out by means of thermal radiation, in particular infrared radiation.

[0029] A preferred further step of the process consists of testing the first and / or second formulation, particularly by metrological means. Testing is carried out, in particular, using an optical testing device. It is preferred that the optical testing device includes a camera. Testing is performed after the first and / or after the second formulation has been taken up. It is particularly preferred that testing is performed after or before the drying step.

[0030] Preferably, the first formulation, which has solidified at least partially to form a microstructure, and preferably the second formulation combined with the first formulation, are demolded. Demolding takes place at and through the first opening of the mold. Preferably, demolding takes place after drying, and particularly preferably after testing. Demolding preferably takes place at the second formulation.

[0031] Demolding is preferably achieved using a cover element. The cover element, in particular, comprises a cover film and is preferably made of one. The cover element is bonded to the first or second formulation. It is preferred that the bond is material-bonded, particularly adhesive. Alternatively or additionally to demolding using a cover element, demolding is achieved by removing, in particular peeling off, the mold element. Preferably, the cover element is the second formulation element, so that demolding is achieved using the second formulation element.

[0032] Preferably, the demolded microstructure is packaged. It is preferred that the packaging is carried out using a blister pack. Particularly preferably, packaging is carried out using blister film.

[0033] The procedure is carried out in particular with a system having one or more features of the system described below.

[0034] The system according to the invention for producing microstructures is in particular a system for producing microarrays. The system is in particular a device. The system is preferably configured to carry out the method described above. It is particularly preferred that the system has one or more of the features described above, in particular the device features described therein. The system has a mold element. The mold element is in particular compressible or elastic. The mold element has at least one mold opening for the microstructures to be produced. The at least one mold opening is in particular a negative mold for the microstructures to be produced. The mold opening corresponds in particular to a cavity. Preferably, the mold opening has a first opening and a second opening, in particular opposite the first opening.The mold opening is preferably open on both sides, so that the mold element has at least one through-opening. It is preferred that the first and second openings open the mold opening towards the environment. Preferably, a fluid connection between the mold opening and the environment is formed through the first and second openings. Furthermore, the system includes a compression device. The compression device is preferably a pressing and / or bending device. The compression device includes a roller, particularly preferably a pressing roller and / or bending roller, and consists in particular of this. The compression device is designed to compress the mold element. In particular, the compression device is arranged and / or designed to exert a pressing force on the mold element and / or to bend the mold element.In a preferred embodiment, the compression device is designed to reduce the volume of the mold opening by compression.

[0035] It is preferred that the compression device has two opposing rollers, in particular compression rollers and / or bending rollers. The rollers are arranged such that the forming element between the rollers is compressible, in particular pressable and / or bendable. The forming element is preferably located between the rollers. In particular, the rollers are arranged offset from each other and / or in the roller guidance direction.

[0036] It is preferred that the system comprises an isolator, preferably aseptic, in which at least the compression device and at least part of the mold element are arranged.

[0037] The form element of the method and / or system according to the invention is in particular a form element according to DE 10 2020 125 484 A1.

[0038] The invention will now be explained in more detail with reference to preferred embodiments and the accompanying drawings.

[0039] They show: Figs. 1a-1d schematic, cutaway side views of manufacturing states to illustrate the method according to the invention, wherein Fig. 1b Figures 2a-2c also show an embodiment of a system for the production of microstructures according to the invention, schematic, cutaway side views of production states to illustrate the method according to the invention, wherein Fig. 2c Fig. 3 shows a schematic, cutaway side view of a manufacturing state to illustrate the inventive method, also showing an inventive embodiment of a system for manufacturing microstructures, Fig. 4 shows a schematic, cutaway side view of a manufacturing state to illustrate an embodiment of the inventive method, and Fig. 5 shows a schematic side view to illustrate an embodiment of the inventive method with a representation of a further inventive embodiment of a system for manufacturing microstructures.

[0040] Similar or identical components or elements are identified in the figures by the same reference numerals or variations thereof (12, 12' and 12"). Particularly for improved clarity, elements that have already been identified are not provided with reference numerals in all figures.

[0041] Fig. 1a Figure 1 shows a forming element 10, which here is specifically designed as an elastic film 11. On the upper surface shown, the film 11 has a first side 16 and, opposite it, a second side 20. Conical or pyramidal forming openings 12 extend through the film 11. On the first side 16, the forming openings 12 have a first opening 14. The forming openings 12 taper from the first side 16 to the second side 20, with a second opening 18 being formed on the second side 20. A first formulation 22, preferably containing an active ingredient, is arranged on the second side 20 in contact with the second openings 18 of the forming openings 12. It is possible (not shown) that some of the formulation 22 is absorbed into the forming openings 12 through the second openings 18 due to capillary action.

[0042] Arrow 52 shows a feed and arrow 54 shows a discharge of the mold element, so that the process can preferably be carried out as a flow process and / or as a roller process.

[0043] Fig. 1b indicates a second state of execution Fig. 1a As schematically represented by arrows 24, pressure has been exerted on the mold element 10 or the film 11. Preferably, the mold element has been compressed. Due to the exertion of pressure, the mold element 10 is compressed, so that the volume of the mold openings 12' is reduced compared to the embodiment made of Fig. 1a The pressure was reduced. The application of pressure can be carried out on one or both sides of the forming element 10 by means of a compression device 37, for example a press device or a rolling device.

[0044] It is shown in Fig. 1b also a system 100 for the production of microstructures with form element 10 and compression device 37. This compression device 37 is in particular a press device.

[0045] Fig. 1c shows another state based on the explanations from the Figuren 1a und 1b .

[0046] An auxiliary element 26, in particular designed as a film, was arranged on the first side 16 of the mold element 10. The auxiliary element 26 closes the first openings 14 of the volume-reduced mold openings 12'.

[0047] Fig. 1d shows a further state of the statements from the Figuren 1a bis 1c Contrary to the statements made in the Figuren 1b bis 1c The mold element 10 has expanded again, in particular relaxed (indicated by arrows 28). It is particularly preferred that the mold element 10 has elastically returned to its original state. Thus, the volume of the mold openings 12 has also expanded again. The expansion of the volume of the mold openings 12 creates a negative pressure within them. Since the first opening 14 of the mold openings 12 is closed, a suction effect is created at the second openings 18. This suction effect draws, in particular sucks, the first formulation 22 into the mold openings 12, so that the mold openings 12 are now partially filled with formulations 22'. It is also possible that, through appropriate dimensioning, the entire mold openings 12 are filled with the first formulation 22. It is also possible that, through hardening of the formulations 22', microstructures, in particular microneedles, are formed within the mold element 10.

[0048] The form element 10 from Fig. 2a This essentially corresponds to the form element 10 of the Figuren 1a bis 1d Unlike the execution of the Figuren 1a bis 1d The tips of the mold openings 12 are located in Fig. 2a in a projection 36 of the form element 10. The second openings 18 of the form elements 12 made of Fig. 2a thus lead into this supernatant 36. The provision of the first formulation 22 takes place in a recess 32 of a formulation element 30 designed as a film 30. The recess 32 is located on a first side 34 of the formulation element 30, and it is preferred that the recess 32 corresponds essentially to a negative shape of the supernatant 36.

[0049] In Fig. 2a The diagram shows that slide 11 of form element 10 and slide 30 of formulation element 30 are merged, in particular linked (merging shown from left to right).

[0050] Fig. 2b shows another state according to the execution from Fig. 2a Forming element 10 and formulation element 30 are connected to each other, such that the protrusion 36 is arranged in the recess 32. Due to capillary action, some of the formulation 22 has entered the tips 42 of the forming openings 12 through secondary openings 18.

[0051] Fig. 2c shows another state, where it is preferred that the execution be made of Fig. 2b fed from the left in the direction of arrow 52.

[0052] By means of a compression device 37, which here has two offset rollers 38, 40, pressure is exerted on the forming element 10 (shown by arrows 23'). The forming element with the associated formulation element 30 runs from left to right (in the direction of arrows 52, 54). The direction of rotation of the rollers 38, 40 is shown by arrows 56. Preferably, roller 38 rotates clockwise and roller 40 counterclockwise. Due to the pressure exerted by the rollers 38, 40 on the mold element 10 (corresponding to arrows 23') and a longitudinal elongation, in particular due to the tensile force of the rollers 38, 40, the elastic mold element 10 is compressed. This compression reduces the volume of the mold openings 12 of the mold element 10. This change in volume of the mold openings 12 is shown in area A.Here, in the area of ​​the mold opening 12", the mold element has already been compressed, so that the volume of the mold opening 12" has been reduced. In the area of ​​the mold opening 12', however, the mold element 10 has not yet been compressed, so that the volume of the mold openings 12' is in its initial state.

[0053] In the area between rollers 38 and 40, an auxiliary element 26, designed as a film, is fed in the direction of arrow 58. The auxiliary element 26 covers the first side 16 of the compressed forming element 10, thus closing the first openings 14" of the volume-reduced forming openings 12".

[0054] After passing through the area between rollers 38, 40, the mold element relaxes, preferably elastically, and returns to its original shape. This is shown in area B. Due to the elastic deformation of the mold element 10, the volume of the mold openings 12 expands. This creates a vacuum in the mold openings 12. The vacuum draws the first formulation 22 in through the second openings 18 of the mold openings 12. The mold opening 12ʺʺ shown on the right has already fully expanded, so that part of the mold openings 12ʺʺ is already completely filled with the first formulation 22ʺʺ. The volume of the mold openings 12‴, however, has not yet fully expanded, so that only part of the formulation 22‴ has been taken in, while part of the formulation 22' remains in the recess 32.By continuing and fully enlarging the mold openings 12‴, this remaining formulation 22' can then also be included.

[0055] It is shown in Fig. 2c also a subsystem 101 for the production of microstructures with compression device 37, forming element 10, auxiliary element 26 and formulation element 30. The compression device 37 is in particular a pressing device. This subsystem 101 corresponds here to an embodiment of a system 100 for the production of microstructures according to the invention.

[0056] Fig. 3 also shows a manufacturing state, preferably that the design is made of Fig. 2b from the left in the direction of arrow 52. During the execution of the Fig. 3 This was in particular an alternative to the version from Fig. 2c The representation of Fig. 3 is related to the representation from Fig. 2c leaning against it.

[0057] By means of a compression device 37, which here has two offset rollers 38, 40, the forming element 10 is bent around the roller 40. The forming element with the associated formulation element 30 is shown running from left to right (in the direction of arrows 52, 54). The direction of rotation of the rollers 38, 40 is shown by arrows 56. Preferably, roller 38 rotates clockwise and roller 40 counterclockwise. Due to the bending of the forming element 10, a compressed area 72, also to be referred to as a compressed fiber, and a stretched area 74, also to be referred to as a stretched fiber, of the forming element 10 are present on both sides of the neutral fiber 70 (shown in area B'). The compression (represented by arrow 76) results in a reduction of the volume 13' in the compressed area of ​​the mold opening 12". In contrast, the volume 13" increases in the stretched area of ​​the mold opening 12".Since the volume fraction of the compressed area is significantly larger compared to the part that lies in the stretched area, the entire volume of the mold opening 12” is reduced.

[0058] In area A', however, the form element 10 has not (yet) been bent, so that the volume of the form openings 12' is (still) in its initial state.

[0059] In the area between rollers 38 and 40, an auxiliary element 26, designed as a film, is fed in the direction of arrow 58. The auxiliary element 26 covers the first side 16 of the compressed forming element 10, thus closing the first openings 14" of the volume-reduced forming openings 12".

[0060] After passing through the area between rollers 38 and 40, the forming element 10 is returned to its unbent initial state. This results in an overall increase in the volume of the mold opening, in contrast to the overall volume reduction in area B'. This creates a vacuum in the mold openings 12. The vacuum draws the first formulation 22 through the second openings 18 of the mold openings 12.

[0061] It is shown in Fig. 3 also a subsystem 101 for the production of microstructures with compression device 37, forming element 10, auxiliary element 26 and formulation element 30. This compression device 37 is in particular a bending device. This subsystem 101 corresponds here to an embodiment of a system 100 for the production of microstructures according to the invention.

[0062] Fig. 4 Figure 1 shows a further state according to a method for producing microstructures according to the invention. A forming element 10 is fed in from the left in the direction of arrow 52. The forming element 10 has several forming openings 12. The underside of the forming element 10 is connected to a formulation element 30. Preferably, the forming element 10 is configured according to the embodiments of the Figuren 1d or 2c The procedure has been carried out, but the auxiliary element 26 has been removed, in particular subtracted.

[0063] In the depicted area C, the mold openings 12' are already partially filled with a first formulation 22', but the area of ​​the pyramid base of the mold openings 12' is empty. A formulation 50, preferably free of active ingredient, was applied to the first side 16 of the mold element 10 in the area of ​​the first openings 14.

[0064] In the direction of arrow 60, a second formulation element 116, which is in particular designed as a film, is fed in, covering the second formulation. Pressure is exerted on the second formulation element 116 via the roller 110, so that a pressing connection is made between the second formulation element 116 and the forming element 10. This forces the second formulation 50 into the empty areas of the forming openings 12'.

[0065] In the depicted area D, the mold openings 12" are thus filled with the second formulation 50'. Therefore, all mold openings 12 are filled with formulations that, particularly after curing, correspond to microstructures.

[0066] Fig. 4 shows a subsystem 103 of a system 100 for the fabrication of microstructures.

[0067] Fig. 5 shows an embodiment of a system 100 according to the invention for the production of microstructures.

[0068] System 100 is arranged in a housing 102. The housing is preferably sterile with respect to the environment. Feeded elements are preferably sterilized before being fed into the housing 102 and / or guided through mouseholes. The housing 102 is, in particular, an insulator. The films are preferably introduced into the system by means of a packaging tube.

[0069] In the direction of arrow 52', a first formulation element 30 is supplied, in particular by means of a packaging tube 31. In the direction of arrow 58, an auxiliary element 26, preferably designed as a film, is supplied. The auxiliary element 26 is supplied in particular in a packaging tube 47.

[0070] The area shown in Box IIc is in particular in accordance with the design from Fig. 2c or Fig. 3 The first formulation 22 is provided via a first formulation dispenser 21, which applies the formulation 22 as droplets 22' to the formulation element 30, in particular to recesses 32 of the formulation element 30.

[0071] Preferably, the auxiliary element 26 is discharged via rollers 108 after section IIc.

[0072] The first formulation 22 is then preferably dried in the mold element 10' using a drying device 104a.

[0073] This is preferably followed by an inspection of the mold element 10", in particular of the preferably solidified formulation 22. The inspection is preferably carried out using a testing device 106a. The testing device is particularly optical in design. The testing device most preferably includes at least one camera.

[0074] The subsequent area III is preferably designed as shown in Fig. 4The second formulation 50 is provided, in particular, by means of a second formulation dispenser 51, which applies the formulation 50 as droplets 50' onto the forming element 10‴. The second formulation element 60 is implemented, in particular, within a packaging tube 118. The second formulation element 60 comprises, in particular, a permeable and / or moisture-absorbing film, and consists, in particular, of this.

[0075] After section III, the forming element 10 is preferably removed via rollers 114. It is particularly preferred that the first formulation element 30 is also removed along with it. However, it is also possible that the first formulation element 30 is removed earlier, at some point after section IIc. During the removal of the forming element 10, the formulations 22, 50, preferably connected to form microstructures 120, are demolded. It is preferred that the microstructures 120 are connected to the second formulation element, for example adhesively, thus enabling the demolding and further processing of the microstructures 120.

[0076] Preferably, the preferably combined formulations 22, 50, corresponding to the microstructures 120 to be produced, are dried before and / or during demolding. Drying can be carried out using a drying device 104b. Additionally or alternatively, air drying through the preferably permeable and / or moisture-absorbing film 60 can also be performed.

[0077] Preferably, the microstructures 120 are inspected after demolding. It is preferred that the inspection is carried out using a testing device 106b. The testing device particularly includes at least one camera.

[0078] The microstructures 120 are then preferably packaged. For this purpose, a blister film 122 is preferably fed in the direction of arrow 62. The feeding is particularly carried out along rollers 126, 128. The blister film 122 has several upwardly open blisters 123.

[0079] In area E, the blister film 128 is connected to the microstructures 120. The microstructures 120 are then incorporated into the blisters 123, resulting in blister-packed microstructures 124. These are then conveyed in the direction of arrow 54.

Claims

1. A method for producing microstructures (120), in particular microarrays, the method comprising the following steps: providing a planar mold element (10), which comprises at least one mold opening (12) for the microstructure (120) to be produced, the at least one mold opening (12) having a first opening (14) and a second opening (18) which, in particular, is located opposite the first opening (14); providing a first formulation (22) at the second opening (18), said formulation preferably containing an active ingredient; generating a negative pressure in the mold opening (12); and taking up the first formulation (22) through the second opening (18) into the mold opening (12) on account of the negative pressure in the mold opening (12), characterized by a further step prior to the step of generating the negative pressure in the mold opening (12): reducing the volume of the mold opening (12), wherein reducing the volume of the mold opening (12) is effected by a compression, in particular a pressing and / or bending, of the mold element (10).

2. The method of claim 1, characterized by the step of: expanding a volume of the mold opening (12) to generate the negative pressure in the mold opening (12).

3. The method according to claim 1 or 2, characterized in that the compression of the mold element (10) is performed using at least one roll (38; 40), preferably two rolls (38, 40) arranged on either side of the mold element (10).

4. The method according to any one of claims 1 to 3, characterized by a further step, preferably prior to the step of generating the negative pressure in the mold opening (12), particularly preferred prior to the expansion of the volume: arranging an auxiliary element (26), in particular comprising an auxiliary film, on a side of the mold element (10) having the first opening.

5. The method according to any one of claims 1 to 4, characterized by a further step, preferably prior to the step of generating the negative pressure in the mold opening (12), particularly preferred prior to the compression of the mold element (10): closing the first opening of the mold opening (12), preferably by means of the auxiliary element (26).

6. The method according to claim 4, characterized by a further step after the taking-up of the first formulation (22) into the first mold opening (12): removing, in particular pulling off the auxiliary element (26) preferably from the mold element (10).

7. The method according to any one of claims 1 to 6, characterized in that the at least one mold opening (12) is cylindrical or conical, preferably with a round, triangular or quadrangular, particularly preferred square cross section, and / or the mold element (10) comprises, in particular consists of a film.

8. The method according to any of claims 1 to 7, characterized in that the mold element (10) is compressible, in particular elastically compressible.

9. The method according to any of claims 1 to 8, characterized by the further steps after the taking-up of the first formulation (22): providing a second formulation (50) at the first opening (14), said second formulation preferably being free of an active ingredient; and taking up the second formulation (50) into the mold opening (12) through the first opening (14), the second formulation (50) preferably bonding with the first formulation (22).

10. The method according to any one of claims 1 to 9, characterized in that providing the first formulation (22) is performed using a first formulation element (30) preferably designed as a film, the first formulation element (30) comprising the first formulation (22); and / or that providing the second formulation (50) is performed using a second formulation element (116) preferably designed as a film, the second formulation element (116) comprising the second formulation (50).

11. The method according to any one of claims 1 to 10, characterized by a further step: demolding the first formulation (22), which has at least partially solidified to form a microstructure (120), and preferably the second formulation (50) at the first opening of the mold opening (12), it being preferred that the demolding is performed using a cover element preferably comprising a cover film, which cover element is in particular substance-bonded with the formulation; and / or the demolding is performed by removing, in particular pulling off the mold element (10).

12. The method according to any one of claims 1 to 11, characterized by a further step: packaging the demolded microstructure (120) using, in particular, a blister element (122) preferably comprising a blister film.

13. The method according to one of claims 1 to 12, characterized in that the method is performed using a system (100) according to claim 14 or 15.

14. A system (100) for producing microstructures (120), in particular for executing a method according to one of claims 1 to 13, comprising a compressible mold element comprising at least one mold opening (12) for the microstructure (120) to be produced, and a compression device (37) preferably comprising at least one roll (38; 40), the compression device being configured to compress the mold element (10).

15. The system according to claim 14, characterized in that the compression device (37) comprises two opposite rolls (38, 40), the rolls (38, 40) being arranged such that the mold element (10) can be compressed between the rolls (38, 40).