Microfluidic system or microfluidic device and method for manufacturing a microfluidic system or microfluidic device
Patent Information
- Authority / Receiving Office
- DE · DE
- Patent Type
- Patents
- Current Assignee / Owner
- DISCO CORP
- Filing Date
- 2017-09-27
- Publication Date
- 2026-07-23
Smart Images
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Abstract
Description
Technical field
[0001] The present invention relates to a method for producing a microfluidic system or a microfluidic device with at least one channel. Furthermore, the present invention relates to a microfluidic system or a microfluidic device with at least one channel. Technical background
[0002] Microfluidic systems and devices are widely used in various technical fields, such as medical applications, biotechnology, chemical engineering, environmental analysis, food quality analysis, measuring instruments, analytical instruments, and the manufacture of flexible electronics. In particular, microfluidic systems and devices, such as micro-total analysis systems (µ-TAS) and labs-on-a-chip (LOC), are used for microreactors and microanalysis systems.
[0003] Such systems and facilities offer the advantage that, by utilizing their microscopic space, the required amount of experimental materials and the resulting amount of waste disposal can be significantly reduced. The systems and facilities are easy to store and transport, and large experimental setups are not necessary. Furthermore, reactions occurring at the microscopic level within such systems and facilities, which allows for the use of a small sample quantity, are typically very rapid, thus considerably reducing the required experimental time.
[0004] In general, such microfluidic systems and devices consist of glass, such as borosilicate glass or quartz glass, polydimethylsiloxane (PDMS) resin, or plastic. These materials are typically processed using photolithography, sandblasting, laser grooving, laser drilling, wet stamping, hot stamping, or similar methods, and are particularly often provided with one or more microfluidic channels.
[0005] However, such established manufacturing processes for microfluidic systems and equipment generally entail considerable costs. Firstly, the materials used, such as glass, are often expensive and difficult to process. Secondly, processes like photolithography, laser grooving, and laser drilling require the use of complex and costly processing equipment. Furthermore, many of the established manufacturing processes are inflexible, meaning they are difficult to adapt to different system and equipment configurations, which further increases manufacturing costs.
[0006] When embossing processes, such as hot embossing, are used to form one or more microfluidic channels in a substrate, problems frequently arise regarding channel deformation and / or substrate material residue on the embossing equipment. These problems severely limit the accuracy of the channel dimensions achievable with such processes, rendering them unsuitable for applications requiring clearly defined channels.
[0007] Therefore, there remains a need for a cost-effective and reliable method for manufacturing a microfluidic system or microfluidic device that allows one or more channels to be formed with a high degree of accuracy. Summary of the invention
[0008] Accordingly, an objective of the present invention is to provide a cost-effective and reliable method for fabricating a microfluidic system or microfluidic device that enables the formation of one or more channels with a high degree of accuracy. Furthermore, the invention aims to provide a microfluidic system or microfluidic device fabricated by such a method. These objectives are achieved by a fabrication method having the technical features of claim 1 and a microfluidic system or microfluidic device having the technical features of claim 18. Preferred embodiments of the invention are set forth in the dependent claims.
[0009] The invention provides a method for producing a microfluidic system or microfluidic device with at least one channel. The method comprises providing a base layer, a deformable intermediate layer, a cover film, and layering the base layer, the intermediate layer, and the cover film such that a rear surface of the intermediate layer is attached to a front surface of the base layer, and a rear surface of the cover film is attached to a front surface of the intermediate layer opposite its rear surface, thereby forming a layered structure comprising the base layer, the intermediate layer, and the cover film. Furthermore, the method comprises applying pressure to the front surface of the intermediate layer by means of the cover film, such that the intermediate layer is deformed, thereby forming the at least one channel.
[0010] The at least one channel is configured to receive experimental materials and samples to be processed and / or analyzed. The at least one channel may be configured to transport experimental materials and samples to be processed and / or analyzed. The at least one channel is a microfluidic channel. The at least one channel may have a length greater than its width. In particular, the length of the at least one channel may be at least twice its width, preferably at least three times its width, and more preferably at least four times its width.
[0011] The microfluidic system or microfluidic device produced by the method according to the invention comprises the layer structure which has the base layer, the intermediate layer and the cover film, wherein the at least one channel is arranged in the layer structure such that it is open to the side of the cover film.
[0012] In the method according to the invention, the at least one channel is formed by applying pressure to the front surface of the intermediate layer through the cover film, thus deforming the intermediate layer. The pressure is therefore not applied directly to the front surface of the deformable intermediate layer. Rather, the pressure is applied indirectly, that is, via the cover film. The cover film is arranged between a pressure-applying means for applying pressure to the front surface of the intermediate layer, such as a punch, a mold, or a forming tool, and the intermediate layer. Therefore, the pressure-applying means does not come into direct contact with the intermediate layer during the deformation process.This ensures that the material of the deformable intermediate layer does not adhere to or stick to the pressure application medium, reliably preventing the formation of residues of the deformable intermediate layer material on the pressure application medium and deformation of the at least one channel. Therefore, the at least one channel can be formed with a high degree of accuracy, for example, with micrometer precision. Furthermore, unwanted variations in the dimensions of the at least one channel are prevented, thus achieving a reliable manufacturing process.
[0013] Furthermore, no expensive and difficult-to-machine materials, such as glass (e.g., borosilicate glass or quartz glass), or complicated, costly processing equipment required for processes like photolithography, laser grooving, and laser drilling are needed. Instead, at least one channel is formed by applying pressure to the front surface of the intermediate layer, thus enabling the use of simple pressure application tools such as stamps, molds, or dies. Since no residue of the deformable intermediate layer material remains on the pressure application tool, its service life can be significantly extended, and maintenance and repair costs are minimized. This provides a cost-effective manufacturing process.
[0014] Furthermore, the method according to the invention can be easily adapted to different system and equipment configurations by appropriately modifying the pressure application means.
[0015] Therefore, the present invention provides a cost-effective and reliable method for producing a microfluidic system or microfluidic device that makes it possible to form one or more channels with a high degree of accuracy.
[0016] The cover film can be expandable. In particular, the cover film can be expandable to twice its original size or more, preferably to three times its original size or more, and more preferably to four times its original size or more.
[0017] The process may also include widening the cover film.
[0018] The top film can be widened if the pressure is applied through the top film to the front surface of the intermediate layer.
[0019] By using an expandable cover film, in particular a cover film that can be expanded to three or four times its original size or more, the at least one channel can be formed with a particularly high degree of accuracy. For example, this method can ensure with particular reliability that the cover film closely follows the profile of a pressure application device, such as a punch, a mold, or a forming tool, so that the at least one channel is formed with particularly high accuracy.
[0020] The intermediate layer can be cured by an external stimulus, such as UV radiation, heat, an electric field, and / or a chemical substance. In this case, the intermediate layer cures, at least to some extent, upon application of the external stimulus. The intermediate layer can be designed to achieve a stiff, hard state after curing. For example, the intermediate layer can be made of a curable resin, a curable adhesive, a curable gel, or the like. Using such a material for the intermediate layer allows for the formation of at least one channel in a particularly simple and efficient manner.
[0021] Preferred examples of UV-curing resins for use as an intermediate layer in the manufacturing process according to the invention are ResiFlat from DISCO Corporation and TEMPLOC from DENKA.
[0022] The method can further include applying an external impulse to the intermediate layer to cure it after the at least one channel has formed. This ensures with particular reliability that the dimensions of the at least one channel are maintained throughout the entire operational lifetime of the microfluidic system or microfluidic device. Therefore, a particularly robust and stable microfluidic system or microfluidic device is provided.
[0023] In the method according to the invention, the base layer, the intermediate layer, and the top layer are first layered, thereby forming the layer structure comprising the base layer, the intermediate layer, and the top layer. Subsequently, after the layer structure has been formed, pressure can be applied to the front surface of the intermediate layer by means of the top layer, so that the intermediate layer is deformed, thereby forming at least one channel. Thus, at least one channel is formed in the layer structure.
[0024] In this way, the manufacturing process can be carried out in a particularly simple and efficient manner. For example, the layered structure, which comprises the base layer, the intermediate layer, and the top layer, can be pre-prepared, stored for later use, and, if required, used to manufacture a microfluidic system or microfluidic device. The layered structure can therefore be produced in large quantities, making its manufacture particularly efficient in terms of both time and cost.
[0025] Alternatively, during the formation of the layer structure, which has the base layer, the intermediate layer and the top layer, pressure can be applied through the top layer to the front surface of the intermediate layer, so that the intermediate layer is deformed, thereby forming at least one channel.
[0026] For example, pressure can be applied to the front surface of the intermediate layer by using a pressure application device that has a base, such as a base substrate, and one or more projections extending from the base, for example, from a flat surface of the base. In this case, the at least one channel is formed by pressing the one or more projections into the intermediate layer, thus deforming the intermediate layer. Before pressing the one or more projections into the intermediate layer, the cover film can be applied to or attached to a side or surface of the base from which the one or more projections extend, such as a front surface of the base.In particular, the cover film can be applied to or attached to this side or surface of the base in such a way that it follows the profile of the protrusions.
[0027] It is particularly preferred that the cover film be compressible, elastic, flexible and / or bendable. This ensures that the cover film reliably conforms to the profile of the projections.
[0028] Subsequently, the side or surface of the base, which has the cover film applied to it or attached to it, can be pressed against the intermediate layer, thereby deforming the intermediate layer through the cover film, so that at least one channel is formed, and at the same time the layer structure is formed.
[0029] In this case, the cover film can be applied or attached with a particularly high degree of accuracy to the side or surface of the base from which the one or more projections protrude, thereby further increasing the accuracy with which the at least one channel is formed.
[0030] For example, the step of applying or attaching the cover film to the printing device can be carried out in a vacuum chamber. In particular, the cover film can be applied or attached to the printing device using a vacuum laminating device. In such a vacuum laminating device, the printing device is positioned, for example, on a clamping table in a vacuum chamber in a state where a rear face of the base is in contact with an upper surface of the clamping table and a front face of the base, from which one or more projections protrude, is facing upwards. The cover film to be applied to the front face of the base can be held at its circumference by a frame, such as an annular frame, and positioned above the front face of the base in the vacuum chamber.An upper part of the vacuum chamber, located above the clamping table and the frame, is provided with an air inlet opening which is closed by an expandable rubber membrane.
[0031] After the pressure-applying agent and the cover sheet are loaded into the vacuum chamber, the chamber is evacuated and air is supplied to the rubber membrane through the air inlet. This causes the rubber membrane to expand into the evacuated chamber. In this way, the rubber membrane is moved downwards into the vacuum chamber, pressing the cover sheet against the base's front face. This allows the cover sheet to be applied tightly to the base's front face, conforming to the profile of the protrusions. Alternatively, the rubber membrane can be replaced by a soft punch or roller. Subsequently, the vacuum in the chamber is released, and the overpressure in the vacuum chamber holds the cover sheet in position against the base's front face.
[0032] The process may involve heating the cover film during and / or after its application to the front of the base. The heating process softens the cover film, ensuring a particularly reliable conformity to the topography of the base's front surface.
[0033] The heating process can be used to attach the cover film to the front of the base. In particular, the heating process can generate an adhesive bond between the cover film and the base. The attachment of the cover film to the base can occur during the heating process itself and / or in a subsequent cooling process. For example, the cover film can be softened by the heating process. Upon cooling, for example to its initial temperature, the cover film can harden again, creating a form-fit and / or material bond with the base.
[0034] The cover film can be heat-resistant up to a temperature of 180 °C or more, preferably up to a temperature of 220 °C or more and more preferably up to a temperature of 250 °C or more.
[0035] The top layer can be heated to a temperature in the range of 60 °C to 150 °C, preferably 70 °C to 140 °C, more preferably 80 °C to 130 °C, and even more preferably 90 °C to 120 °C. It is particularly preferred that the top layer be heated to a temperature of approximately 100 °C.
[0036] The cover film can be heated for a period of time in the range of 30 seconds to 10 minutes, preferably 1 minute to 8 minutes, more preferably 1 minute to 6 minutes, even more preferably 1 minute to 4 minutes and even more preferably 1 minute to 3 minutes during and / or after the application of the cover film to the base.
[0037] The cover film can be heated directly and / or indirectly.
[0038] The cover film can be heated by applying heat directly to it, for example, using a heat application device such as a heated roller, a heated punch, or the like, or a heat radiation device. The cover film and the pressure application device can be arranged in a receptacle or chamber, such as a vacuum chamber, and an internal volume of the receptacle or chamber can be heated so that the cover film is heated. The receptacle or chamber can be equipped with a heat radiation device.
[0039] The top sheet can be heated indirectly, for example by heating the printing agent before, during, and / or after applying the top sheet to the base. For example, the printing agent can be heated by placing it on a support or carrier, such as a clamping table, and then heating the support or carrier.
[0040] Additionally or as an alternative, the cover film can be attached to the front of the base using an adhesive, such as an adhesive layer.
[0041] The adhesive layer can have a thickness in the range of 5 to 200 µm, preferably 10 to 150 µm and even more preferably 20 to 100 µm.
[0042] The adhesive can be applied only to a circumferential area of the side or surface of the base from which the one or more projections protrude, such as the front of the base. This ensures with particular reliability that, after the pressure-applying agent is removed from the layer structure, no adhesive residue remains in the base area where the projections are formed. Furthermore, adhesive residue is avoided in the at least one channel.
[0043] Furthermore, by applying the adhesive only to the circumference of the area where the top layer and the printing agent are in contact, the area is significantly reduced. Therefore, the printing agent can be more easily removed from the layer structure after the formation of at least one channel.
[0044] The adhesive can be cured by an external stimulus, such as heat, UV radiation, an electric field, and / or a chemical substance. This allows the pressure-applicating agent to be removed from the layer structure particularly easily after the formation of at least one channel. The external stimulus can be applied to the adhesive, reducing its adhesive strength and thus facilitating its easy removal.
[0045] For example, the adhesive can be provided in a ring-shaped arrangement in the circumferential area of the side or surface of the base from which the one or more projections protrude, such as the front of the base.
[0046] The at least one channel can have a width in the range of 5 to 800 µm, preferably 10 to 600 µm, more preferably 20 to 400 µm and even more preferably 50 to 200 µm.
[0047] The at least one channel can have a depth in the range of 5 to 200 µm, preferably 10 to 150 µm and more preferably 20 to 100 µm.
[0048] The at least one channel can have a length in the range of 0.5 to 100 mm, preferably 1 to 80 mm, more preferably 2 to 60 mm and even more preferably 5 to 50 mm.
[0049] The at least one channel can have a substantially straight or straight shape. The at least one channel can have a curved shape, such as a bent, wavy, or corrugated shape. The at least one channel can have a shape that is a combination of the above-mentioned shapes.
[0050] The at least one channel can extend over 5% or more, preferably 10% or more, more preferably 15% or more, even more preferably 20% or more, and even more preferably 30% or more of the width of the layer structure. The length of the at least one channel can be 5% or more, preferably 10% or more, more preferably 15% or more, even more preferably 20% or more, and even more preferably 30% or more of the width of the layer structure.
[0051] The at least one channel can extend over 5% or more, preferably 10% or more, more preferably 15% or more, even more preferably 20% or more, and even more preferably 30% or more of the length of the layer structure. The length of the at least one channel can be 5% or more, preferably 10% or more, more preferably 15% or more, even more preferably 20% or more, and even more preferably 30% or more of the length of the layer structure.
[0052] The layered structure, comprising the base layer, the intermediate layer, and the top layer, has a thickness in the layering direction, that is, in the direction in which the base layer, the intermediate layer, and the top layer are stacked or arranged one on top of the other. The length and width of the layered structure lie along directions perpendicular to the layering direction.
[0053] The width and / or depth of the at least one channel can be constant or vary along the length of the at least one channel.
[0054] The at least one channel extends in or along a plane of the layered structure, that is, a plane of the layered structure that is perpendicular to the layering direction. The at least one channel can extend to one or more lateral or transverse edges of the layered structure. The lateral directions of the layered structure are perpendicular to the layering direction.
[0055] At least one channel does not extend along the entire thickness of the layer structure.
[0056] The method according to the invention can be a method for producing a microfluidic system or a microfluidic device with multiple channels. Pressure can be applied through the cover film to the front surface of the intermediate layer, causing the intermediate layer to deform and thereby forming the multiple channels.
[0057] The microfluidic system or microfluidic device can have two or more channels, three or more channels, four or more channels, five or more channels, or six or more channels.
[0058] The microfluidic system or microfluidic device may have 50 or fewer channels, 40 or fewer channels, 30 or fewer channels, 20 or fewer channels, or 10 or fewer channels.
[0059] At least two of the multiple channels can be connected to each other.
[0060] The channels can be identical to each other, for example with regard to their shapes and / or dimensions. At least some of the channels can differ from each other, for example with regard to their shapes and / or dimensions.
[0061] As explained above, pressure can be applied through the cover film to the front surface of the intermediate layer by using a pressure application device, such as a stamp, mold, or forming tool. The pressure application device may have a base, such as a base substrate, and one or more projections extending from the base, for example, from a flat surface of the base.
[0062] The base and the one or more projections can be made of the same material or of different materials.
[0063] In particular, the base and / or the one projection or the multiple projections can be made of a stiff, hard material, such as a metal, a plastic, a ceramic or a semiconductor, for example Si.
[0064] For example, the one or more protrusions on a side or surface of a base substrate, such as one made of one of the materials mentioned above, can be formed by cutting the side or surface of the substrate, for example, by cutting grooves and / or notches into the side or surface. This cutting process can be carried out, for example, by mechanical cutting, such as using a blade or a saw, or by laser cutting.
[0065] The at least one channel can be formed by pressing one or more projections over the top layer into the intermediate layer, i.e., with the top layer positioned between them, so that the intermediate layer is deformed. This process can be carried out during and / or after the formation of the layer structure comprising the base layer, the intermediate layer, and the top layer.
[0066] If the intermediate layer is curable by an external stimulus, such as UV radiation, heat, an electric field, and / or a chemical substance, it can be cured by applying this stimulus while one or more protrusions are pressed into the intermediate layer. In this way, at least one channel can be formed with a particularly high degree of accuracy. After the intermediate layer has cured, the pressure-applying agent can be removed from the layer structure.
[0067] The intermediate layer can be cured after the pressure application agent has been removed from the layer structure.
[0068] This approach allows for particularly easy removal of the pressure-applying agent.
[0069] The top layer facilitates the removal of the pressure-sensitive adhesive from the layer structure, for example, before or after the intermediate layer has cured. In particular, the presence of the top layer allows the pressure-sensitive adhesive to be removed from the layer structure reliably and easily, preventing residues of the intermediate layer, such as resin, adhesive, or gel residues, from adhering to the pressure-sensitive adhesive.
[0070] The material of the base layer is not particularly restricted. Preferably, the base layer consists of a rigid material, such as polyethylene terephthalate (PET) and / or silicon and / or glass and / or stainless steel.
[0071] For example, if the base layer is made of PET or glass and the intermediate layer is curable by an external impulse, the intermediate layer can be cured with radiation that can be transmitted through PET or glass, such as UV radiation. Although glass is generally a difficult material to process, the method according to the invention does not require any processing of the base layer. Furthermore, the base layer can be selected to have a small thickness, thus keeping material costs low. If the base layer is made of silicon or stainless steel, a particularly cost-effective base layer is provided.
[0072] The base layer can also be made from a combination of the materials listed above.
[0073] The base layer can have a thickness in the range of 200 to 1500 µm, preferably 400 to 1200 µm and more preferably 500 to 1000 µm.
[0074] The intermediate layer can consist of a resin, an adhesive, a gel, or the like. In particular, the intermediate layer can consist of a curable resin, a curable adhesive, a curable gel, or the like.
[0075] The intermediate layer can have a thickness in the range of 20 to 1000 µm, preferably 50 to 800 µm, more preferably 100 to 600 µm, even more preferably 150 to 500 µm and even more preferably 200 to 400 µm.
[0076] The outer film can be made of a polymer material, such as polyvinyl chloride (PVC), polyolefin (PO), or ethylene vinyl acetate (EVA). For example, the outer film can be a material similar to "Saran" wrapping film.
[0077] The cover film can have a thickness in the range of 5 to 200 µm, preferably 8 to 100 µm, more preferably 10 to 80 µm, and even more preferably 12 to 50 µm. This ensures with particular reliability that the cover film is flexible and pliable enough to conform adequately to the profile of a printing agent, while simultaneously exhibiting a high degree of robustness.
[0078] The method may further include cutting the layer structure, which has the base layer, the intermediate layer and the top layer, after forming at least one channel along the thickness direction of the layer structure, in order to obtain several microfluidic systems and / or microfluidic devices.
[0079] The invention further provides a microfluidic system or microfluidic device with at least one channel, wherein the microfluidic system or microfluidic device has a layered structure comprising a base layer, an intermediate layer, and a top layer. A rear surface of the intermediate layer is attached to a front surface of the base layer, and a rear surface of the top layer is attached to a front surface of the intermediate layer opposite its rear surface. The at least one channel is configured in the layered structure such that it is open towards the side of the top layer.
[0080] The features described above for the manufacturing process according to the invention also apply to the microfluidic system or microfluidic device according to the invention. In particular, the base layer, the intermediate layer, and the top layer of the microfluidic system or microfluidic device according to the invention can each be the base layer, the intermediate layer, and the top layer described above for the manufacturing process according to the invention.
[0081] The microfluidic system or microfluidic device according to the invention is a microfluidic system or microfluidic device that is produced by the method according to the invention.
[0082] Therefore, the microfluidic system or microfluidic device according to the invention offers the technical effects and advantages that have already been described in detail above for the manufacturing process according to the invention.
[0083] In the microfluidic system or microfluidic device according to the invention, the thickness of the intermediate layer in the region or regions of the layer structure in which the at least one channel is formed is less than the thickness of the intermediate layer in the region or regions of the layer structure in which no channel is formed. The thickness of the intermediate layer in the region or regions of the layer structure in which the at least one channel is formed is less than the thickness of the intermediate layer in the region or regions of the layer structure that surrounds the at least one channel. The at least one channel results from this change in the thickness of the intermediate layer.
[0084] The microfluidic system or microfluidic device according to the invention can be configured to process and / or influence a fluid or fluids using the at least one channel, for example, to transport, mix, and / or separate them. The microfluidic system or microfluidic device according to the invention can be configured to process and / or influence small quantities of a fluid or fluids, particularly on the order of microliters, using the at least one channel, for example, to transport, mix, and / or separate them.
[0085] The microfluidic system or microfluidic device according to the invention can be used to receive experimental materials and samples to be treated and / or analyzed. The microfluidic system or microfluidic device according to the invention can be used to transport experimental materials and samples to be treated and / or analyzed. The microfluidic system or microfluidic device according to the invention can be used to treat and / or analyze experimental materials and samples. The microfluidic system or microfluidic device according to the invention can be used for some or all of the above-mentioned purposes.
[0086] The microfluidic system or microfluidic device according to the invention can be used in various technical fields, such as medical applications, biotechnology, chemical process engineering, environmental analysis, food quality analysis, measuring instruments, analytical fields, and the manufacture of flexible electronics. The microfluidic system or microfluidic device according to the invention can be used for a microreactor and / or a microanalysis system. For example, the microfluidic system or microfluidic device according to the invention can be a micro-total analysis system (µ-TAS) and / or a lab-on-a-chip (LOC). List of characters
[0087] Non-limiting examples of the invention are discussed below with reference to the drawings, wherein: Fig. 1 is a perspective view showing a first embodiment of a pressure application means to be used for the manufacturing process according to the present invention; Fig. 2 is a perspective view showing a second embodiment of a pressure application means to be used for the manufacturing process according to the present invention; Fig. 3 a schematic cross-sectional representation of the in Fig. The pressure application device shown in section 2 is; Fig. 4 is a cross-sectional view showing one step of applying a cover film to the in Fig. 2 pressure application means shown in a manufacturing process according to an embodiment of the present invention; Fig. 5 is a cross-sectional representation that shows the result of the in Fig. 4 illustrated installation steps are shown; Fig. 6 is a cross-sectional representation illustrating a step of pressing the pressure application means, to which the cover film is attached, against an intermediate layer in the manufacturing process according to the embodiment of the present invention; Fig. 7 is a cross-sectional representation that shows the result of the in Fig. 6 illustrated pressure application steps are shown; Fig. 8 is a cross-sectional representation illustrating a step of the curing of the intermediate layer in the manufacturing process according to the embodiment of the present invention; Fig. 9 is a cross-sectional representation illustrating a step of removing the printing agent from a layer structure comprising a base layer, an intermediate layer and a top film in the manufacturing process according to the embodiment of the present invention; Fig. 10 is a cross-sectional representation illustrating a step of cutting the layer structure in the manufacturing process according to the embodiment of the present invention; Fig. 11. A top view is shown through the Fig. Figure 10 illustrates the microfluidic system or microfluidic device obtained in the cutting step; Fig. 12 a cross-sectional view of the microfluidic system or microfluidic device that is or were incorporated into Fig. 11 is shown; Fig. 13 an enlarged view of the circled area in Fig. 12 is; and Fig. 14 a cross-sectional representation of a layer structure comprising a base layer, an intermediate layer and a top layer, for use in a manufacturing process according to a further embodiment of the present invention. Detailed description of preferred embodiments
[0088] Preferred embodiments of the present invention are described below with reference to the accompanying drawings. The preferred embodiments relate to methods for manufacturing microfluidic systems or microfluidic devices and microfluidic systems or microfluidic devices manufactured by these methods.
[0089] Fig. Figure 1 is a perspective view showing a first embodiment of a pressure application device. 2 , which can be used for the manufacturing process according to the present invention. The pressure application means 2 is in the form of a mold or a forming tool.
[0090] The pressure application agent 2 has a base 3 , that is, a base substrate, and several projections 5 , which from the base 3protrude, that is, stand out from a flat surface of the base 3 protrude, the projections 5 are on a front 3a the base 3 trained.
[0091] The base 3 In a top view, it has a circular shape. All projections 5 are identical in shape and point towards the pressure application device in a top view 2 essentially a Y-shape (see Fig. 1) Furthermore, all projections 5 the same dimensions, that is, the same length, width and height.
[0092] The base 3 and the protrusions 5 They are made of the same material. The base material 3 and the protrusions 5 is a stiff, hard material, such as a metal, a plastic, a ceramic or a semiconductor, such as Si.
[0093] The protrusions5 can be found on the front 3a the base 3 formed by a cutting process, such as mechanical cutting, for example using a blade or a saw, or laser cutting, as explained above.
[0094] Fig. Figure 2 is a perspective view showing a second embodiment of a pressure application device. 2 , which can be used for the manufacturing process according to the present invention. The pressure application agent is also shown. 2 According to the second embodiment, it is in the form of a mold or a forming tool.
[0095] The pressure application agent 2 According to the second embodiment, it differs from the pressure application device. 2 According to the first embodiment, with regard to the shape of the base and the structure of the projections. In describing the second embodiment of the pressure application device... 2Elements that are essentially identical to or similar to those of the first embodiment are designated by the same reference numerals, and a repeated more detailed description of the same is omitted.
[0096] As in Fig. As shown in 2, the base 3 of the pressure application agent 2 According to the second embodiment, a rectangular shape is visible in a top view. Two different types of projections. 5a , 5b are on a front 3a the base 3 trained. The first advantages 5a are identical in shape and point towards the pressure application device in a top view 2 essentially a Y-shape. The second protrusions 5b are identical in shape and point towards the pressure application device in a top view 2a wavy shape with a branched end section (see Fig. 2) Furthermore, all first projections 5a have the same dimensions and all feature second projections 5b the same dimensions.
[0097] Due to the provision of the two different types of protrusions 5a , 5b on the front 3a the base 3 can that in Fig. 2 pressure application devices shown 2 It can be used to manufacture several different microfluidic systems or devices in a single process, each featuring different types of channels, as detailed below. Therefore, this pressure application agent can 2 They are particularly advantageous for the mass production of such systems and facilities.
[0098] The shape of the base 3 is not particularly limited and can, for example, be a circular shape (see Fig. 1), an oval shape or a polygonal shape, such as a rectangular shape (see Fig. 2) or a square shape.
[0099] The shapes and dimensions of the protrusions 5 , 5a , 5b The shapes and dimensions of the channel(s) to be formed are selected based on the desired shape(s). These shapes and dimensions are essentially identical to those of the projections. 5 , 5a , 5b , which makes it possible to form the channel or channels with a high degree of accuracy.
[0100] Fig. 3 is a schematic cross-sectional representation of the in Fig. 2 pressure application devices shown 2 . Specifically shows Fig. 3. a cross-section along the long side of the rectangular base 3and through the section of the base 3 , in which the second projections 5b are arranged. It should be noted that for the sake of simplicity and better clarity, only ten sections of the projections are shown. 5b in the cross-sectional view of the Fig. 3 are shown. As further shown in Fig. As shown in 3, the base 3 a back 3b on, whose front 3a opposite.
[0101] The following describes a method for producing a microfluidic system or a microfluidic device according to an embodiment of the present invention by using the Fig. 2 pressure application devices shown 2 with reference to Fig. 4 to Fig. 13 described.
[0102] First, a top film is applied. 4 provided (see Fig. 4) The cover film 4 has a front surface 4aand a rear surface 4b on. The cover film 4 It can be made of a polymer material, such as polyvinyl chloride (PVC), polyolefin (PO), or ethylene vinyl acetate (EVA). For example, the cover film can be a material similar to "Saran" wrapping film.
[0103] The cover film 4 can have a thickness in the range of 5 to 200 µm, preferably 8 to 100 µm, more preferably 10 to 80 µm and even more preferably 12 to 50 µm.
[0104] The cover film 4 It is flexible and pliable, so that it can be reliably ensured that the cover film 4 the profile of the protrusions 5a , 5b adapts. The top film is particularly preferred. 4 expandable, for example to twice its original size or more, three times its original size or four times its original size or more.
[0105] An adhesive layer 9 is applied to the front surface 4a the cover film 4 applied. The adhesive layer 9 can have a thickness in the range of 5 to 200 µm, preferably 10 to 150 µm and even more preferably 20 to 100 µm.
[0106] The adhesive layer 9 is only in a circumferential area of the cover film 4 as provided for, as in Fig. 4 is shown. For example, the adhesive layer 9 have a ring shape. The adhesive layer 9 serves to protect the cover film 4 on a frame 10 , such as a ring-shaped frame. By applying the cover film. 4 on the frame 10 in this way (see Fig. 4) the handling of the cover film 4 subsequent procedural steps are facilitated. However, the use of a framework, such as the frame 10, for handling the cover film 4 purely optional. Furthermore, the adhesive layer serves 9 to add the cover film 4 on the front 3a the base 3 to be affixed as follows with reference to Fig. 5 is executed.
[0107] The adhesive of the adhesive layer 9 It can be hardened by an external stimulus, such as heat, UV radiation, an electric field, and / or a chemical substance. In this way, the printing agent can be... 2 After the formation of the multiple channels, they can be removed particularly easily. An external impulse can be applied to the adhesive to reduce its adhesive strength, thus facilitating easy removal of the pressure-applying agent. 2 is made possible.
[0108] After applying the cover film 4 on the frame 10 through the adhesive layer 9 will the cover film 4on the front 3a the base 3 of the in Fig. 2 pressure application devices shown 2 appropriate as in Fig. 4 is indicated by an arrow. Before applying the cover film. 4 on the front 3a the base 3 The pressure application agent 2 on a clamping table 12 , for example in a vacuum chamber, arranged in a state in which the back 3b the base 3 with an upper surface of the clamping table 12 is in contact and the front 3a the base 3 , from which the projections 5a , 5b protrude, is directed upwards (see Fig. 4).
[0109] As mentioned above, the step of applying the cover film can 4 on the front 3a the base 3 in a vacuum chamber. In particular, the cover film can be4 by using a vacuum lamination device, for example in the manner discussed above, on the front side 3a the base 3 be applied. If the cover film 4 If it is expandable, it will expand when it is at the front. 3a the base 3 is attached.
[0110] The result of the in Fig. The illustrated installation step 4 is in Fig. 5 shown. As shown in this latter drawing, the cover film 4 so at the front 3a the base 3 It was appropriate that they matched the profile of the protrusions 5a , 5b closely follows. Therefore, in a subsequent phase of the manufacturing process according to the present embodiment, channels can be formed with a particularly high degree of accuracy.
[0111] The cover film 4 is caused by the adhesive layer 9 on the front3a the base 3 appropriate. As also in Fig. As shown in section 5, this is the adhesive layer. 9 only in a circumferential area of the front 3a This is provided for. Therefore, it can be reliably ensured that after the removal of the pressure-applying agent, 2 no residues of the adhesive layer 9 in the area of the front 3a remain, in which the projections 5a , 5b are trained. Furthermore, adhesive residues are removed from the pressure-applying agent. 2 Channels to be trained were avoided.
[0112] Furthermore, by providing the adhesive layer 9 only in the circumference of the front 3a the area where the cover film 4 and pressure application devices 2 The dimensions of the parts attached to each other via the adhesive are significantly reduced. Therefore, the pressure application agent can 2They can be removed more easily after the channels have formed.
[0113] In addition to or as an alternative to applying the cover film 4 on the front 3a the base 3 through the adhesive layer 9 can the cover film 4 on the front 3a can be applied by removing the top film 4 during and / or after the application of the top film 4 on the front 3a is heated. Furthermore, the cover film can 4 Such a heating process softens the surface, thereby ensuring particularly reliable protection of the top film. 4 the topography of the front 3a adapts.
[0114] An adhesive force between the cover film 4 and 3 This can be generated by the heating process, as discussed above. Applying the top film 4 at the base 3This can occur during the heating process itself and / or in a subsequent cooling process of the cover film. 4 This can be achieved. For example, the top film can 4 The heating process softens the film. Upon cooling, for example back to its initial temperature, the top film can... 4 harden again, for example so that a form fit and / or a material bond with the base 3 is generated.
[0115] The cover film 4 It can be heat-resistant up to a temperature of 180 °C or more, preferably up to a temperature of 220 °C or more, and more preferably up to a temperature of 250 °C or more. During the heating process, the cover film can 4 The product is heated to a temperature in the range of 60 °C to 150 °C, preferably 70 °C to 140 °C, more preferably 80 °C to 130 °C, and even more preferably 90 °C to 120 °C. The cover film is particularly preferred. 4heated to a temperature of approximately 100 °C.
[0116] During the heating process, the top film can 4 over a period of time ranging from 30 seconds to 10 minutes, preferably 1 minute to 8 minutes, more preferably 1 minute to 6 minutes, even more preferably 1 minute to 4 minutes and even more preferably 1 minute to 3 minutes during and / or after the application of the top film 4 on the front 3a the base 3 be heated.
[0117] The cover film 4 It can be heated directly and / or indirectly, as discussed above. For example, the top film can be heated. 4 by heating the pressure application medium 2 before and / or during and / or after applying the top film 4 on the front 3a the base 3 They are heated indirectly. The pressure application agent 2 can be achieved by heating the clamping table 12 be heated (see Fig. 4).
[0118] Alternatively, the cover film can be used 4 in a different way, apart from heating the cover film 4 and / or the use of the adhesive layer 9 on the front 3a the base 3 can be applied. In particular, the cover film can be... 4 without using an adhesive on the front 3a the base 3 be attached.
[0119] Furthermore, a base layer is 7 and a deformable intermediate layer 13 provided (see Fig. 6).
[0120] The material of the base layer 7 is not particularly restricted. Preferably the base layer consists 7 made of a rigid material, such as polyethylene terephthalate (PET) and / or silicon and / or glass and / or stainless steel. The base layer 7can have a thickness in the range of 200 to 1500 µm, preferably 400 to 1200 µm and more preferably 500 to 1000 µm.
[0121] The intermediate layer 13 It can be formed from a resin, an adhesive, a gel, or the like. The intermediate layer 13 can have a thickness in the range of 20 to 1000 µm, preferably 50 to 800 µm, more preferably 100 to 600 µm, even more preferably 150 to 500 µm and even more preferably 200 to 400 µm.
[0122] The intermediate layer 13 It can be cured by an external stimulus, such as UV radiation, heat, an electric field, and / or a chemical substance. Therefore, the intermediate layer hardens. 13 when the external impulse is applied to it, at least to a certain extent. The intermediate layer 13It can be designed to achieve a stiff, hard state after curing. Preferred examples of UV-curing resins for use as an intermediate layer. 13 are ResiFlat from DISCO Corporation and TEMPLOC from DENKA.
[0123] The base layer 7 and the intermediate layer 13 are layered in such a way that a rear surface of the intermediate layer 13 on a front surface of the base layer 7 is attached. A rear surface 7b the base layer 7 , which is opposite its front surface (see Fig. 8), is on an upper surface of a pad 14 , such as a clamping table, arranged (see Fig. 6) A front surface 13a the intermediate shift 13 , which is opposite its rear surface, is arranged so that it points upwards.
[0124] The pressure application agent is described below. 2 , where the cover film 4 is attached against the front surface 13a the intermediate shift 13 pressed, as in Fig. Figure 6 is illustrated by an arrow. In this way, the top layer 4 Pressure on the front surface 13a the intermediate shift 13 applied so that the intermediate layer 13 is deformed, creating multiple channels 20 be trained (see Fig. 9) Specifically, the protrusions 5a , 5b into the intermediate shift 13 pressed, whereby the cover film 4 is arranged in between, so that the intermediate layer 13 is deformed.
[0125] Furthermore, pressing the pressure-applying device 2 , where the cover film 4 is attached against the front surface 13a the intermediate shift 13the rear surface 4b the cover film 4 on the front surface 13a the intermediate shift 13 attached, thereby forming a layered structure which forms the base layer 7 , the intermediate layer 13 and the cover film 4 has. Therefore, in the method according to the present embodiment, the channels 20 during the formation, that is, at the same time as the formation of the layer structure, which is the base layer 7 , the intermediate layer 13 and the cover film 4 exhibits, trained.
[0126] Fig. 7 is a cross-sectional view showing the result of the Fig. The 6 illustrated pressure application steps are shown. The rear surface 7b the base layer 7 is parallel to the back 3b the base 3 of the pressure application agent 2 , as in Fig. 7 is indicated by dashed arrows. Therefore, the channels 20 trained in a particularly precise and uniform manner.
[0127] Subsequently, the external impulse, such as UV radiation, heat, an electric field and / or a chemical substance, is applied to the intermediate layer. 13 agitated, as in Fig. 8 is indicated by arrows to show the intermediate layer 13 to harden.
[0128] The intermediate layer will be specifically 13 by applying the external impulse to it, while the projections 5a , 5b into the intermediate shift 13 They are pressed down, then hardened. This occurs through the hardening of the intermediate layer. 13 Can the application between the cover film 4 and intermediate layer 13 will be increased further.
[0129] If the base layer 7 consists of PET or glass and the intermediate layer 13The intermediate layer can be cured by radiation. 13 They can be cured with radiation that can be transmitted through PET or glass, such as UV radiation. In this case, the radiation can be emitted from the side of the back surface. 7b the base layer 7 be applied (see Fig. 8) For example, ResiFlat from DISCO Corporation and TEMPLOC from DENKA can be used as UV-curing resins for the intermediate layer. 13 be used.
[0130] After the intermediate layer has hardened 13 The pressure application agent 2 removed from the layered structure, as in Fig. 9 is indicated by an arrow.
[0131] If the adhesive of the adhesive layer 9Since the adhesive can be cured by an external impulse, such as heat, UV radiation, an electric field and / or a chemical substance, this impulse can be applied to the adhesive to reduce its adhesive strength, thus making the pressure-applying agent particularly easy to remove. 2 is made possible by the layered structure.
[0132] As further in Fig. As shown in Figure 9, the layer structure comprises several layers within it formed by the pressure application medium. 2 trained channels 20 The channels 20 are structured in such a way that they face the side of the top film 4 are open.
[0133] After removing the pressure-applying agent 2 The layer structure is cut along its thickness direction, as shown in Fig. 10 is indicated by dashed vertical lines. In this way, several microfluidic systems and / or microfluidic facilities are represented. 30 (see Fig. 11) received.
[0134] Furthermore, the microfluidic systems and / or microfluidic facilities 30 through this cutting process from the adhesive layer 9 and the framework 10 separated.
[0135] Fig. Figure 11 is a top view showing a microfluidic system or microfluidic facility 30 shows that or the through the in Fig. The cutting step illustrated in point 10 was obtained. The microfluidic system or microfluidic device 30 is a microfluidic system or microfluidic device according to an embodiment of the present invention.
[0136] The microfluidic system or microfluidic facility 30 has a channel20 on, whose shape and dimensions are essentially identical to those of the second projections 5b are. Specifically, the canal indicates 20 in a top view of the microfluidic system or microfluidic device 30 a wavy shape with a branched end section. Therefore, the channel consists of 20 effectively consisting of two channels connected to each other, the first channel being the wavy section of the channel 20 and consists of a straight branch of the branched end section, and the second channel consists of the other straight branch of the branched end section. The branched end section of the channel 20 It can be used, for example, to separate and / or mix a fluid or fluids, especially small quantities of a fluid or fluids, for example on the order of microliters.
[0137] The canal 20It is designed to receive and transport experimental materials and samples for treatment and / or analysis. The channel 20 is a microfluidic channel.
[0138] The canal 20 The channel can have a width in the range of 5 to 800 µm, preferably 10 to 600 µm, more preferably 20 to 400 µm, and even more preferably 50 to 200 µm. 20 The channel can have a depth in the range of 5 to 200 µm, preferably 10 to 150 µm and more preferably 20 to 100 µm. 20 can have a length in the range of 0.5 to 100 mm, preferably 1 to 80 mm, more preferably 2 to 60 mm and even more preferably 5 to 50 mm.
[0139] Fig. Figure 12 is a cross-sectional representation of the microfluidic system or microfluidic facility 30 along the dotted line in Fig. 11. Fig. Figure 13 is an enlarged view of the circled area in Fig. 12. As in Fig. As shown in section 13, the canal extends 20 not along the entire thickness of the intermediate layer 13 .
[0140] According to a further embodiment of the manufacturing process of the present invention, the base layer can be 7 , the intermediate layer 13 and the cover film 4 They are first layered, creating the layered structure that forms the base layer. 7 , the intermediate layer 13 and the cover film 4 exhibits, is formed. Such a layered structure is found in Fig. 14 shown. Optionally, an adhesive layer can be applied. 9 essentially in the same way as discussed above, applied to the front surface 4a the cover film 4 to be applied. The adhesive layer 9 can be used to remove the cover film 4 on a frame, such as the frame 10, to be applied to facilitate handling of the layer structure in subsequent process steps. However, the adhesive layer can 9 can also be omitted.
[0141] Subsequently, after the formation of the layer structure, the top film can be used. 4 Pressure on the front surface 13a the intermediate shift 13 to be applied in order to create the intermediate layer 13 to deform, thereby altering the channels 20 are formed in the layered structure.
[0142] The process of applying pressure to the front surface 13a the intermediate shift 13 can be done in essentially the same way as discussed above, that is, by using the pressure application device. 2 , are carried out. The approach according to the present embodiment differs from the one described above with reference to Fig. 4 to Fig. 13 described mainly in that the cover film 4 at the intermediate shift 13 instead of the pressure application device 2 appropriate when the pressure application device 2 against the intermediate shift 13 is pressed.
[0143] If the cover film 4 If it is expandable, it will expand when pressure is applied through the cover film. 4 on the front surface 13a the intermediate shift 13 is applied.
[0144] Subsequent steps of curing the intermediate layer 13 , of removing the pressure-applying agent 2 The layer structure and the cutting of the layer structure can be described in the same way as above, with reference to Fig. 8 to Fig. 10 described to be carried out.
Claims
[1] Method for manufacturing a microfluidic system or microfluidic device (30) having at least one channel (20), the method comprising: Provide a base layer (7); Providing a deformable intermediate layer (13); Provide a cover sheet (4); Layers of the base layer (7), the intermediate layer (13) and the top sheet (4), such that a rear surface of the intermediate layer (13) is attached to a front surface of the base layer (7) and a rear surface (4b) of the top sheet (4) is attached to a front surface (13a) of the intermediate layer (13) opposite its rear surface, thereby forming a layer structure comprising the base layer (7), the intermediate layer (13) and the top sheet (4); and Applying pressure to the front surface (13a) of the intermediate layer (13) by the cover film (4) so that the intermediate layer (13) is deformed, thereby forming the at least one channel (20). [2] Method according to claim 1, wherein the cover film (4) is expandable and the method further comprises expanding the cover film (4). [3] Method according to claim 2, wherein the cover film (4) is expanded when the pressure is applied through the cover film (4) to the front surface (13a) of the intermediate layer (13). [4] Method according to any of the preceding claims, wherein the intermediate layer (13) can be cured by an external impulse, such as UV radiation, heat, an electric field and / or a chemical substance. [5] Method according to claim 4, further comprising, after forming the at least one channel (20), applying the external impulse to the intermediate layer (13) so that the intermediate layer (13) is cured. [6] Method according to one of the preceding claims, wherein the base layer (7), the intermediate layer (13) and the top sheet (4) are first layered, thereby forming the layer structure comprising the base layer (7), the intermediate layer (13) and the top sheet (4), and subsequently pressure is applied by the top sheet (4) to the front surface (13a) of the intermediate layer (13) so that the intermediate layer (13) is deformed, thereby forming the at least one channel (20). [7] Method according to any of the preceding claims, wherein the at least one channel (20) has a width in the range of 5 to 800 µm and / or a depth in the range of 5 to 200 µm and / or a length in the range of 0.5 to 100 mm. [8] Method according to any of the preceding claims, wherein the at least one channel (20) extends over 5% or more, preferably 10% or more, of a width and / or a length of the layer structure. [9] Method according to any of the preceding claims, wherein the microfluidic system or microfluidic device (30) has several channels (20) and the pressure is applied through the cover film (4) to the front surface (13a) of the intermediate layer (13) so that the intermediate layer (13) is deformed, thereby forming the several channels (20). [10] Method according to claim 9, wherein at least two of the multiple channels (20) are connected to each other. [11] Method according to one of the preceding claims, wherein the pressure is applied through the cover film (4) to the front surface (13a) of the intermediate layer (13) using a stamp, a mold or a forming tool. [12] Method according to any of the preceding claims, wherein the base layer (7) consists of a rigid material, such as polyethylene terephthalate and / or silicon and / or glass and / or stainless steel. [13] Method according to any of the preceding claims, wherein the base layer (7) has a thickness in the range of 200 to 1500 µm. [14] Method according to any of the preceding claims, wherein the intermediate layer (13) is formed from a resin, an adhesive or a gel. [15] Method according to any of the preceding claims, wherein the intermediate layer (13) has a thickness in the range of 20 to 1000 µm. [16] Method according to any of the preceding claims, wherein the cover film (4) consists of a polymer material such as polyvinyl chloride, polyolefin or ethylene vinyl acetate. [17] Method according to any of the preceding claims, wherein the cover film (4) has a thickness in the range of 5 to 200 µm. [18] Microfluidic system or microfluidic device (30) having at least one channel (20), wherein the microfluidic system or microfluidic device (30) comprises: a layered structure comprising a base layer (7), an intermediate layer (13) and a top sheet (4); wherein a rear surface of the intermediate layer (13) is attached to a front surface (17) of the base layer (7) and a rear surface (4b) of the top sheet (4) is attached to a front surface (13a) of the intermediate layer (13) opposite its rear surface, and at least one channel (20) is formed in the layer structure in such a way that it is open to the side of the cover film (4).