Method and System for Producing Microstructures

Abstract

The invention relates to a method for producing microstructures, the method including providing a planar mold element, which includes at least one mold opening for the microstructure to be produced, wherein the at least one mold opening has a first opening and a second opening; providing a first formulation at the second opening; generating a negative pressure in the mold opening; and taking up the first formulation through the second opening into the mold opening on account of the negative pressure in the mold opening. The invention further relates to a system for producing microstructures.

Claims

1. A method for producing microstructures, in particular microarrays, the method comprising the following steps: providing a planar mold element, which comprises at least one mold opening for the microstructure to be produced, the at least one mold opening having a first opening and a second opening which, in particular, is located opposite the first opening; providing a first formulation at the second opening, said formulation preferably containing an active ingredient; generating a negative pressure in the mold opening; and taking up the first formulation through the second opening into the mold opening on account of the negative pressure in the mold opening.

2. The method of claim 1, comprising the step of: expanding a volume of the mold opening to generate the negative pressure in the mold opening.

3. The method according to claim 1, comprising by a further step prior to the step of generating the negative pressure in the mold opening in particular prior to the expansion of the volume of the mold opening: reducing the volume of the mold opening.

4. The method according to claim 3, comprising by a compression, in particular a pressing and/or bending, of the mold element to reduce the volume of the mold opening.

5. The method according to claim 4, wherein the compression of the mold element is performed using at least one roll, preferably two rolls arranged on either side of the mold element.

6. The method according to claim 1, comprising a further step, preferably prior to the step of generating the negative pressure in the mold opening, particularly preferred prior to the expansion of the volume: arranging an auxiliary element, in particular comprising an auxiliary film, on a side of the mold element having the first opening.

7. The method according to claim 1, comprising a further step, preferably prior to the step of generating the negative pressure in the mold opening, particularly preferred prior to the compression of the mold element: closing the first opening of the mold opening, preferably by means of the auxiliary element.

8. The method according to claim 6, comprising a further step after the taking-up of the first formulation into the first mold opening: removing, in particular pulling off the auxiliary element preferably from the mold element.

9. The method according to claim 1, wherein the at least one mold opening is cylindrical or conical, preferably with a round, triangular or quadrangular, particularly preferred square cross section.

10. The method according to claim 1, wherein the mold element comprises, in particular consists of a film.

11. The method according to claim 1, wherein the mold element comprises is compressible, in particular elastically compressible.

12. The method according to claim 1, comprising further steps after the taking-up of the first formulation: providing a second formulation at the first opening, said second formulation preferably being free of an active ingredient; and taking up the second formulation into the mold opening through the first opening, the second formulation preferably bonding with the first formulation.

13. The method according to claim 1, wherein providing the first formulation is performed using a first formulation element preferably designed as a film, the first formulation element comprising the first formulation; and/or that providing the second formulation is performed using a second formulation element preferably designed as a film, the second formulation element comprising the second formulation.

14. The method according to claim 1, comprising a further step: Demolding the first formulation, which has at least partially solidified to form a microstructure, and preferably the second formulation at the first opening of the mold opening.

15. The method according to claim 14, wherein 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.

16. The method according to claim 1, comprising a further step: packaging the demolded microstructure using, in particular, a blister element preferably comprising a blister film.

17. The method according to claim 1, wherein the method is performed using a system.

18. A system for producing microstructures, in particular for executing a method according to claim 1, comprising a compressible mold element comprising at least one mold opening for the microstructure to be produced, and a compression device preferably comprising at least one roll, the compression device being configured to compress the mold element.

19. The system according to claim 18, wherein the compression device comprises two opposite rolls, the rolls being arranged such that the mold element can be compressed between the rolls.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The terms Fig., Figs., Figure, and Figures are used interchangeably in the specification to refer to the corresponding figures in the drawings.

[0039] In the following, the invention is described in more detail by means of preferred embodiments with reference to the accompanying drawings.

[0040] In the drawings:

[0041] FIGS. 1a-1d are schematic sectional side views of production states showing the method according to the invention, with FIG. 1b also showing an embodiment of a system for producing microstructures according to the invention,

[0042] FIGS. 2a-2c are schematic sectional side views of production states showing the method according to the invention, with FIG. 2c also showing an embodiment of a system for producing microstructures according to the invention,

[0043] FIG. 3 is a schematic sectional side view of a production state showing the method according to the invention, while also showing an embodiment of a system for producing microstructures according to the invention,

[0044] FIG. 4 is a schematic sectional side view of a production state showing an embodiment of the method according to the invention, and

[0045] FIG. 5 is a schematic sectional side view of a production state showing an embodiment of the method according to the invention and showing another embodiment of a system for producing microstructures according to the invention.

DESCRIPTION OF THE INVENTION

[0046] In the Figures, similar or identical components or elements are identified by the same reference numerals or variations thereof (12, 12 and 12). In particular in the interest of improved clarity, preferably elements already identified are not provided with reference numerals in all Figures.

[0047] FIG. 1a shows a mold element 10 which, in the present instance, is designed in particular as a film 11. At the upper surface illustrated, the film 11 has a first side 16 and an opposite second side 20. Conical or pyramidal mold openings 12 extend through the film 11. On the first side 16, the mold openings 12 have a first opening 14. The mold openings 12 taper, starting from the first side 16, to the second side 20, with a second opening 18 being formed on the second side 20. On the second side 20, a first formulation 22, preferably containing an active ingredient, is arranged in contact with the second openings 18 of the mold openings 12. It is possible (though not illustrated) that a part of the formulation 22 is received in the mold openings 12 through the second openings 18 due to capillary effects.

[0048] Arrow 52 illustrates a supply, arrow 54 a discharge of the mold element, so that the method can preferably be implemented as a plow process and/or as a roll process.

[0049] FIG. 1b illustrates a second state of the embodiment in FIG. 1a. Illustrated schematically by the arrows 24 is a pressure that 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 has been reduced when compared to the embodiment in FIG. 1a. The pressure can be exerted using a compression device 37, e.g. a press device or a roll device, on one or on both sides of the mold element 10.

[0050] FIG. 1b also illustrates a system 100 for producing microstructures with a mold element 10 and a compression device 37. This compression device 37 is in particular a press device.

[0051] FIG. 1c illustrates another state in accordance with the embodiments in FIGS. 1a and 1b.

[0052] An auxiliary element 26, in particular designed as a film, has been arranged on the first side 16 of the mold element 10. Here, the auxiliary element 26 closes the first openings 14 of the mold openings 12 reduced in volume.

[0053] FIG. 1d illustrates a further state of the embodiments in FIGS. 1a to 1c. In contrast to the embodiments in FIGS. 1b to 1c, the mold element 10 has expanded again, in particular relaxed (illustrated by arrows 28). It is particularly preferred that the mold element 10 has restored itself elastically ba expanding. Thus, the volume of the mold openings 12 has expanded again. The expansion of the volume of the mold openings 12 causes a negative pressure in the mold openings 12. Since the first opening 14 of the mold openings 12 is closed, a suction effect is created at the second openings 18. Due to the suction effect, the first formulation 22 was taken up, in particular sucked into the mold openings 12, so that the mold openings 12 are now partially filled with formulations 22. It is also possible, by corresponding dimensioning, to fill the entire mold openings 12 with the first formulation 22. It is possible that by solidification of the formulations 22 microstructures, in particular microneedles, are formed in the mold element 10.

[0054] The mold element 10 of FIG. 2a corresponds substantially to the mold element 10 of FIGS. 1a to 1b. Different from the embodiment in FIGS. 1a to 1d, the tips of the mold openings 12 in FIG. 2a are located in a protrusion 36 of the mold element 10. The second openings 18 of the mold elements 12 of FIG. 2a thus end in this protrusion 36. The first formulation 22 is provided in a depression 32 of a formulation element 30 designed as a film 30. The depression 32 is located on a first side 34 of the formulation element 30, it being preferred that the depression 32 corresponds substantially to a negative mold of the protrusion 36.

[0055] FIG. 2a shows that the film 11 of the mold element 10 and the film 30 of the formulation element 30 are combined, in particular connected (combining illustrated from left to right).

[0056] FIG. 2b illustrates another state of the embodiment in FIG. 2a. Here, the mold element 10 and the formulation element 30 are combined so that the protrusion 36 is arranged in the depression 32. Due to capillary effects a part of the formulation 22 has entered the tips 42 of the mold openings 12 through the second openings 18.

[0057] FIG. 2c shows another state, it being preferred that the embodiment of FIG. 2b is supplied from the left in the direction of the arrow 52.

[0058] The compression device 37, which in the present instance comprises two offset rolls 38, 40, exerts pressure on or compresses the mold element 10 (as illustrated by arrows 23). As illustrated, the mold element with the formulation element 30 connected thereto extends from the left to the right (in the direction of the arrows 52, 54). The direction of rotation of the rolls 38, 40 is illustrated by the arrows 56. As illustrated, it is preferred that the roll 38 rotates clockwise and the roller 40 rotates counterclockwise. Due to the pressure exerted by the rolls 38, 40 on the mold element 10 (corresponding to the arrows 23), as well as to a longitudinal expansion, caused in particular by the tensile force of the rolls 38, 40, the elastic mold element 10 is compressed. Due to this compression, the volume of the mold openings 12 of the mold element 10 decreases. This change in the volume of the mold openings 12 is illustrated in the region A. Here, the mold element has already been compressed in the region of the mold opening 12, so that the volume of the mold opening 12 is reduced. In the region of the mold opening 12, however, the mold element 10 is not yet compressed, so that the volume of the mold openings 12 is in the initial state.

[0059] As illustrated, an auxiliary element 26 is supplied in the region between the rolls 38, 40 in the direction of the arrow 58. Here, the auxiliary element 26 covers the first side 16 of the compressed mold element 10, so that the first openings 14 of the mold openings 12 reduced in volume are closed.

[0060] After having passed the region between the rolls 38, 40, the mold element relaxes, preferably restores itself elastically. This is illustrated in region B. Due to the elastic deformation of the mold element 10, the volume of the mold openings 12 expands. This results in a negative pressure in the mold openings 12. Due to the negative pressure, the first formulation 22 is drawn through the second openings 18 of the mold openings 12. The mold opening 12 shown on the right has already fully expanded, so that a part of the mold openings 12 is already completely filled with the first formulation 22. In contrast to this, the volume of the mold openings 12m has not yet fully expanded, so that only a part of the formulation 22 has been taken up, while a part of the formulations 22 remains in the depression 32. When the mold openings 12m are moved on and fully expanded, this remaining formulation 22 can also be taken up.

[0061] FIG. 2c also illustrates a subsystem 101 for producing microstructures with a compression device 37, a mold element 10, an auxiliary element 26 and a formulation element 30. This compression device 37 is in particular a press device. The subsystem 101 corresponds to an embodiment of a system 100 for producing microstructures according to the invention.

[0062] FIG. 3 also shows a production state, it being preferred that the embodiment in FIG. 2b is supplied from the left in the direction of the arrow 52. The embodiment in FIG. 3 is, in particular, an alternative to the embodiment in FIG. 2c. The illustration in FIG. 3 is analogous to the illustration FIG. 2c.

[0063] The compression device 37, which in the present instance comprises two offset rolls 38, 40, bends the mold element 10 about the roll 40. As illustrated, the mold element with the formulation element 30 connected thereto extends from the left to the right (in the direction of the arrows 52, 54). The direction of rotation of the rolls 38, 40 is illustrated by the arrows 56. As illustrated, it is preferred that the roll 38 rotates clockwise and the roller 40 rotates counterclockwise. By bending the mold element 10, a compressed portion 72, also referred to as a compressed strand, and a stretched portion 74, also referred to as a stretched strand, of the mold element 10 exist on either side of the neutral strand 70 (as illustrated in region B). The compression (illustrated by arrow 76) causes a reduction of the volume 13 in the compressed portion of the mold opening 12. In the stretched portion of the mold opening 12, however, an increase of the volume 13 is caused. Since the volume fraction of the compressed portion is significantly larger when compared to the portion located in the stretched portion, a reduction of volume of the mold opening 12 is effected in total.

[0064] In the region A, however, the mold element 10 is not (yet) bent, so that the volume of the mold openings 12 is (still) in the initial state.

[0065] As illustrated, an auxiliary element 26 is supplied in the region between the rolls 38, 40 in the direction of the arrow 58. Here, the auxiliary element 26 covers the first side 16 of the compressed mold element 10, so that the first openings 14 of the mold openings 12 reduced in volume are closed.

[0066] After having passed through the region between the rolls 38, 40, the mold element 10 is restored to the unbent initial state. Thereby, an increase in total volume of the mold opening occurs, contrary to the reduction in total volume in region B. This results in a negative pressure in the mold openings 12. Due to the negative pressure, the first formulation 22 is drawn through the second openings 18 of the mold openings 12.

[0067] FIG. 3 also illustrates a subsystem 101 for producing microstructures comprising a compression device 37, a mold element 10, an auxiliary element 26 and a formulation element 30. This compression device 37 is in particular a bending device. The subsystem 101 corresponds to an embodiment of a system 100 for producing microstructures according to the invention.

[0068] FIG. 4 shows another state according to a method for producing microstructures according to the invention. A mold element 10 is supplied from the left in the direction of the arrow 52. The mold element 10 comprises a plurality of mold openings 12. The lower side of the mold element 10 is connected to a formulation element 30. It is preferred that the mold element 10 is implemented according to the embodiments in FIG. 1d or 2c, however, with the auxiliary element 26 removed, in particular pulled off.

[0069] In the region C illustrated, the mold openings 12 are already partially filled with a first formulation 22, while, however, the region of the pyramid base of the mold openings 12 is empty. A formulation 50, preferably free of active ingredients, has been applied on the first side 16 of the mold element 10 in the region of the first openings 14.

[0070] A second formulation element 116, which is in particular designed as a film, is supplied in the direction of the arrow 60, the element covering the second formulation. Pressure is exerted on the second formulation element 116 via the roll 110, so that the second formulation element 116 is connected to the mold element 10 by being pressed onto the same. Thereby, the second formulation 50 is pressed into the empty portions of the mold openings 12.

[0071] In the region D illustrated, the mold openings 12 are thus filled with the second formulation 50. Thus, the mold openings 12 are all filled with formulations which, in particular after solidification, correspond to microstructures.

[0072] FIG. 4 shows a subsystem 103 of a system 100 for producing microstructures.

[0073] FIG. 5 shows an embodiment of a system 100 for producing microstructures according to the invention.

[0074] The system 100 is arranged in a housing 102. The housing is preferably sterile with respect to the environment. Elements supplied are preferably sterilized before being supplied and/or are passed into the housing 102 through mouseholes. In particular, the housing 102 is an insulator. The films are preferably introduced into the system using a packaging tube.

[0075] A first formulation element 30 is supplied in the direction of the arrow 52, in particular using a packaging tube 31. An auxiliary element 26, preferably designed as a film, is supplied in the direction of the arrow 58. The auxiliary element 26 is supplied, in particular, in a packaging tube 47.

[0076] The region illustrated in box IIc is designed, in particular, corresponding to the embodiment in FIG. 2c or FIG. 3. Here, the first formulation 22 is provided through a first formulation dispenser 21 which applies the formulation 22 as droplets 22 on the formulation element 30, in particular into depressions 32 of the formulation element 30.

[0077] Behind the region IIc, the auxiliary element 26 is preferably discharged via rollers 108.

[0078] Subsequently, the first formulation 22 in the mold element 10 is preferably dried using a drying device 104a.

[0079] This is preferably followed by a testing of the mold element 10, in particular of the preferably solidified formulation 22. The testing is preferably performed by means of a test device 106a. The test device is in particular configured as an optical device. It is particularly preferred that the test device comprises at least one camera.

[0080] The adjoining region III is preferably designed as illustrated in FIG. 4. The second formulation 50 is provided in particular using a second formulation dispenser 51 which applies the formulation 50 as droplets 50 onto the mold element 10m. The second formulation element 60 is supplied in particular using a packaging tube 118. The second formulation element 60 comprises, in particular consist of in particular a permeable and/or moisture-absorbing film.

[0081] Downstream of the region III, the mold element 10 is preferably discharged via rollers 114. It is particularly preferred in this context that the first formulation element 30 is discharged along therewith. However, it is also possible that the first formulation element 30 is discharged already at an earlier time, i.e. sometime after the region IIc. Upon discharging the mold element 10, the formulations 22, 50, which are preferably bonded to form microstructures 120, are demolded. It is preferred in this context that the microstructures 120 are connected, e.g. adhesively, to the second formulation element and that the demolding and further transport of the microstructures 120 is thus performed.

[0082] Prior to and/or during demolding, the preferably connected formulations 22, 50, which correspond to the microstructures 120 to be produced, are preferably dried. Drying can be performed using the drying device 104b. In addition or as an alternative, however, air drying can also be performed using the preferably permeable and/or moisture-absorbing film 60.

[0083] Preferably, the microstructures 120 are tested after deforming. It is preferred that the testing is performed using the test device 106b. The test device comprises in particular at least one camera.

[0084] Subsequently, the microstructures 120 are preferably packaged. To this end, it is preferred to supply a blister film 122 in the direction of the arrow 62. The supply is performed in particular over rollers 126, 128. The blister film 122 comprises a plurality of blisters 123 open to the top.

[0085] In the region E, the blister film 128 is joined with the microstructures 120. In doing so, the microstructures 120 are received in the blisters 123, so that blister-packaged microstructures 124 are obtained. These are discharged in the direction of the arrow 54.