SYSTEM WITH A MICROFLUIDIC CARTRIDGE AND A CARTRIDIC COVERING DEVICE FOR SEALING THE MICROFLUIDIC CARTRIDGE AND METHOD FOR ITS MANUFACTURING
Patent Information
- Application Number
- DE502019012960
- Authority / Receiving Office
- DE · DE
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2018-07-31
- Filing Date
- 2019-07-31
- Publication Date
- 2025-03-06
- Estimated Expiration
- 2039-07-31
Description
Technical area
[0001] The present invention relates to a system comprising a microfluidic cartridge and a cartridge cover device for sealing the microfluidic cartridge, as well as a method for producing the system.
[0002] The terms used in the following explanations are to be understood as follows: "Adhesive film" refers to any form of flat adhesive system, i.e. not only adhesive tapes in the narrower sense, but also adhesive films, adhesive strips, adhesive plates or adhesive die-cut parts.
[0003] "Pressure-sensitive adhesive" refers to adhesive bonds in which the two parts are joined together by an intermediate adhesive layer and under pressure. The bond is reversible in that it can be removed again without damaging the two parts, because the adhesive seam is the weakest point in the joint.
[0004] "Structural" adhesive bonds are those in which the joining partners are joined in such a way that, if separated, the bond is not necessarily released at the adhesive seam, but under certain circumstances, one of the joining partners may be the weakest point in the bond and is then damaged by the separation. Structural adhesive bonds therefore possess high strength. The strengths, measured in quasi-static tensile-shear tests, are over 6 MPa for structural bonds. Typical values aimed for structural adhesive bonds with epoxy adhesives are 30 MPa. In this case, UV radiation refers to radiation in the wavelength range of UV light, particularly "UVA" or "UVC" light. UVA radiation is in the wavelength range of approximately 100 nm.380 to 315 nanometers (nm), UVC radiation is in the wavelength range of approximately 280 to 100 nm. Generally, both are electromagnetic radiation with wavelengths shorter than visible light. For UVA light, the energy input is approximately 3.26 to 3.95 electron volts (eV), while for UVC light, it is approximately 4.43 to 12.40 eV.
[0005] "Activation" means that the adhesive begins to cure after exposure to UV light. This means that the photoinitiators contained in the adhesive are activated by light and initiate the curing process by initiating the formation of polymer chains. UV-curing adhesives are typically irradiated after the bonding partners have been joined. This requires substrates that are sufficiently permeable to the UV radiation used. The bonding area is then irradiated until curing has progressed sufficiently.
[0006] "Open time" or "open time" is the time between adhesive application and bonding. For UV-activated adhesives, the open time is understood to be the time between UV activation and bonding, i.e., the time after activation during which a bond can be established. During the open time, for example, a cartridge cover is applied to a cartridge to be sealed. The adhesive contained in the cartridge cover ensures the necessary adhesion. Since the viscosity, i.e., the thickness of an adhesive, generally increases after application, the open time for adhesives is limited.
[0007] The "curing time" is the period between the joining of the joining partners and the achievement of the final strength of the bond.
[0008] The term "dark reaction" refers to the fact that a curing reaction is initiated (triggered) by briefly irradiating the adhesive with UV light and then complete curing takes place without further irradiation.
[0009] A "cover layer" refers to a layer applied to an adhesive that permanently covers the cartridge. The cover layer can remain permanently in place to protect the cartridge cover device. Alternatively, the cover layer can be provided in the form of a release liner that is removed prior to use, i.e., prior to joining to a cartridge. State of the art
[0010] Microfluidic systems in the form of polymeric test carriers are used for in vitro diagnostics or for diagnostic monitoring of a variety of diseases. The test carriers typically contain a microfluidic system that allows for the automated processing of a biological assay.
[0011] The production of a test carrier requires the provision of a cartridge, which is manufactured, for example, using a microthermoforming or injection molding process. The cartridge is then filled with the reagents (solid and liquid) required for the desired function. Finally, the cartridge is sealed with a foil seal.
[0012] Common techniques for sealing cartridges include cold sealing, thermal diffusion sealing, laser welding, and solvent sealing. In cold sealing (adhesive), an acrylic-based film is applied to the cartridge. Pressure is applied to break microcapsules, thus creating adhesion only in the desired areas. Adhesive bonding is easy to implement, but can lead to clogging of the cartridge's microfluidic channels and has relatively low seal strength and durability, especially at higher temperatures.
[0013] Thermal diffusion sealing is characterized by high seal strength. However, the process carries the risk of negative influences from the sealing temperature when using thermosensitive reagents. Furthermore, the availability of suitable commercially available sealing films is limited.
[0014] Laser welding is easy to implement from a process perspective, but is not yet technically mature for transparent / transparent materials and is associated with high acquisition costs.
[0015] Solvent sealing can achieve high seal strengths. Due to the solvents used (usually toxic), solvent sealing is difficult to handle, requires a secure workstation (fume hood), and can negatively influence biochemical reagents.
[0016] WO 2017 / 117163 A1 shows a two-stage structural pressure-sensitive adhesive.
[0017] US 2015 / 0184034 A1 shows an adhesive layer and an adhesive film.
[0018] WO 2017 / 174303 A1 discloses a pressure-sensitive adhesive tape which contains a radiation-activatable, polymerizable composition which undergoes a dark reaction after activation.
[0019] From US 2003 / 0081090 A1 a cover for print cartridges is known, which is applied to the print cartridge by means of an adhesive.
[0020] From WO 2018 / 153985 A1, an adhesive film is known which comprises an adhesive mass which can be activated by UV radiation and which, after UV activation, has an open time of 10 seconds to 60 minutes, during which the film has a pressure-sensitive adhesive property.
[0021] D. Kosse, et al., "Microthermoforming and Sealing of COP Films to Form Thin Walled Labon-achip Cartridges," Proceedings of the 8th International Conference on Multi-Material Micro Manufacture, 2011, pp. 187-190, discloses a method for adhesively sealing microfluidic cartridges using a COC-based adhesive. Description of the invention
[0022] Based on the known prior art, it is an object of the present invention to provide an improved device for closing a microfluidic cartridge and a corresponding method.
[0023] This object is achieved by a system comprising a microfluidic cartridge and a cartridge cover device for sealing the microfluidic cartridge having the features of claim 1 and a method for producing the system having the features of claim 10. Advantageous further developments emerge from the subclaims.
[0024] A first aspect of the invention relates to a system comprising a microfluidic cartridge and a cartridge cover device for sealing the microfluidic cartridge, wherein the cartridge cover device comprises at least one layered adhesive. According to the invention, the layered adhesive is UV-activated to initiate curing and, after activation, is pressure-sensitively adhesive until the expiration of an open time at room temperature. Alternatively, the layered adhesive can also be pressure-sensitively adhesive prior to UV activation.
[0025] Because the layered adhesive is pressure-sensitive in its unactivated state before the open time has elapsed, the cartridge cover can be treated like a "normal" pressure-sensitive adhesive tape during processing. This means that it can be easily applied with adhesive and, if necessary, removed or even repositioned before the end of the open time. Only after the open time has elapsed are the joining partners finally and structurally bonded.
[0026] The cartridge cover device for sealing a microfluidic cartridge comprises at least one layered adhesive, which comprises: 2-40 wt.% film former, 10-70 wt.% aromatic epoxy resins, cycloaliphatic epoxy resins, with the cycloaliphatic epoxy resins not exceeding 35 wt.%, 0.5-7 wt.% cationic initiators, 0-50 wt.% epoxidized polyether compounds, and 0-20 wt.% polyol, with the total amount being 100%. Surprisingly, it was found that the composition of the layered adhesive, whose curing is initiated by UV activation, results in this layered adhesive being pressure-sensitive during the open time and ultimately leading to structural bond strength after the end of the open time.
[0027] A beneficial component of the layered adhesive is a film former. The film former can be a thermoplastic or elastomeric polymer compound that regulates viscosity. The following polymers can be used as film formers: acrylates, polyamides, phenoxy resins, polyurethanes, or ethylene-vinyl acetates (EVAs), with polyurethanes and ethylene-vinyl acetate copolymers being preferred. Aromatic, aliphatic, and cycloaliphatic epoxy resins can be used as epoxy resins. They can have a viscosity ranging from liquid to high-viscosity, or solid. The proportion of aromatic resins, measured as the proportion of the epoxy equivalent of the mixture, is preferably higher than the proportion of cycloaliphatic epoxy resins. In a further development, the proportion of the epoxy equivalent of the cycloaliphatic epoxy resins to the epoxy equivalent of all epoxy resins is between 0% and 35%.
[0028] In a further development, the proportion of the epoxy equivalent of the aromatic epoxy resins to the epoxy equivalent of all epoxy resins is over 60%.
[0029] With such recipes, open times of up to 60 minutes are generally possible.
[0030] Advantageously, the layered adhesive contains at least one polyether compound derivatized with epoxy groups. These are particularly preferably epoxidized polyethylene glycols or polypropylene glycols. In a further development, the proportion of the epoxy equivalent of the epoxidized polyether compounds relative to the epoxy equivalent of all epoxy resins is between 0 and 40%. The open time can be effectively adjusted by varying the proportion of polyether compounds.
[0031] Another component of the layered adhesive can be compounds with multiple free hydroxyl groups (polyols), such as polyethylene glycols, polytetrahydrofuran, or polypropylene glycols. According to the literature, the addition of polyols is responsible for delaying the curing reaction (A. Hartwig, "Kationisch härtende Epoxidharzklebstoffe," February 2012). Transfer reactions prolong the curing reaction, resulting in a dark reaction. Together with the epoxidized polyethers, the polyols are therefore useful for controlling the open time and the rate of the crosslinking reaction.
[0032] Cationic photoinitiators can be used as initiators for the layered adhesive. Suitable examples include arylsulfonium, iodonium, ferrocenium, or thioxathenium salts, with triarylsulfonium salts being particularly preferred. These are characterized by a rapid decomposition reaction even at relatively low UV radiation. When the initiators decompose, acids are formed that cure the epoxy resins.
[0033] Other components that may be used for the layered adhesive include additives for epoxy adhesive tapes that are known to those skilled in the art: impact modifiers, organic or inorganic fillers, and functional fillers such as flame retardants, dyes, anti-aging agents, flow and rheology aids.
[0034] In a preferred development, the layered adhesive mass after UV activation has an open time of 0 seconds to 60 minutes, preferably of 0 seconds to 30 minutes and particularly preferably of 10 seconds to 60 minutes, while the film has a pressure-sensitive adhesive property.
[0035] Preferably, the layered adhesive cures after UV activation without the application of heat or UV light. In a further embodiment, the layered adhesive forms a thermoset film during curing.
[0036] In another embodiment, the layered adhesive, after curing, adheres only to the surfaces of the microfluidic cartridge made of substrates such as COP, PC, or ABS. Advantageously, the layered adhesive is no longer adhesive at the locations of the channels.
[0037] In a further development, a reactive epoxy resin system allows a thin adhesive layer to be sufficient to achieve a very high sealing force. This can have the advantage that the channels of the cartridge are not blocked by the adhesive: the thinner the adhesive thickness, the lower the risk of the channels being blocked by the adhesive. In a further embodiment, the layered adhesive has a thickness of 2 to 1,000 µm, alternatively a thickness of 5 to 500 µm, a thickness of 5 to 200 µm, or a thickness of 5 to 100 µm. It is advantageous if the thickness is selected so that sufficient adhesive strength is provided while simultaneously preventing the channels from becoming blocked by the layered adhesive. Thinner layered adhesive thicknesses have the advantage, among other things, that less adhesive needs to be used.
[0038] In a further embodiment, the layered adhesive comprises fillers. The fillers can be, among other things, ceramic fillers or, alternatively, polymer-based fillers. For example, the fillers can be solid glass spheres, hollow glass spheres, and / or polymer spheres. Advantageously, the maximum dimension of a filler, alternatively the diameter of a filler, or alternatively the smallest diameter of a filler is smaller than the thickness of the layered adhesive. The fillers can, among other things, have a beneficial effect on the elastic properties of the layered adhesive or on the elastic properties of the cartridge cover device, which in turn can lead to advantageous sealing of the microfluidic cartridge. The addition of fillers can also lead to the layered adhesive or, alternatively, the entire cartridge cover device being able to be produced comparatively more economically.
[0039] In a further embodiment, a cover layer, preferably a plastic film, which functions as a covering film, is arranged on a first side of the layered adhesive. The cover layer can, for example, also assume the function of a carrier material. In addition, the cover layer can increase the stability of the cartridge covering device, in particular if the cover layer remains in the device during use of the microfluidic cartridge. In addition, the cover layer can protect the layered adhesive, for example from external influences such as chemical, physical, or mechanical influences. The cover layer can also be advantageous in that it allows the cartridge covering device to be rolled up without the layered adhesive unfavorably sticking to itself.In addition, the cover layer can allow several separate cartridge cover devices to be placed on top of each other without the layered adhesives sticking together in an unfavorable manner.
[0040] In a preferred embodiment, the cover layer is removable. For example, the cover layer can be a peel-off film or a release liner. This allows the cover layer to be removed again after the cartridge cover device has been joined to the microfluidic cartridge or after the layered adhesive has cured. This is advantageous, for example, when high quality requirements exist for the optical properties of the cartridge cover device.
[0041] Curing of the layered adhesive is initiated by UV activation. During curing, a thermoset film is formed. The cured layered adhesive preferably has the required stability and / or resistance to external influences, particularly chemical, physical, or mechanical influences.
[0042] In an advantageous further development, the layered adhesive has a thickness of > 5 µm, > 100 µm, > 500 µm or > 1000 µm.
[0043] In a further embodiment, a cover layer, which can preferably function as a release film, is arranged on a second side of the layered adhesive. This cover layer can also serve as a carrier material. In addition, the cover layer protects the layered adhesive from external influences, for example, chemical, physical, and / or mechanical influences. This cover layer can also be advantageous in that it allows the cartridge cover device to be rolled up without the layered adhesive unfavorably sticking to itself, or because it allows several separate cartridge cover devices to be placed on top of one another without the layered adhesives unfavorably sticking to one another.
[0044] The cover layer can be designed to be removable. For example, the cover layer can be a peel-off film or a release liner. The cover layer can then be removed before merging the cartridge cover device with the microfluidic cartridge.
[0045] In a further development, the cover layer has an adhesive-repellent coating on the side facing the layered adhesive and / or the side facing away from the layered adhesive. The adhesive-repellent coating on the side facing the layered adhesive can be particularly advantageous if the cover layer is to be removable. The adhesive-repellent coating on the side facing away from the layered adhesive can be advantageous if the cartridge cover device is to be rollable.
[0046] In a further development, the adhesive-repellent coating is a silicone system, in particular a silicone layer, with which the cover layer is coated. Advantageously, the adhesive-repellent coating is selected so that it exhibits sufficient dehesion to the layered adhesive.
[0047] In a further development, the cover layer on the first side of the layered adhesive and / or the cover layer on the second side of the layered adhesive is a temperature- and media-resistant film, preferably a PET film, a PC film, a COP film, or the like. The temperature-resistant films preferably withstand temperatures greater than 80°C, particularly preferably from 90°C to 125°C. The media resistance of the films can be classified, for example, according to the DIBt test list.
[0048] In a further development, the cartridge cover device exhibits autofluorescence in the range of 230 to 450 nm. Autofluorescence in the range of 300-450 nm can be achieved with a cartridge cover device that, in addition to a layered adhesive, has at least one cover layer, such as a carrier film.
[0049] In a further development, the layered adhesive of the cartridge cover device exhibits significant autofluorescence only in the range of 300 to 450 nm. This property is particularly advantageous for in vitro diagnostics, which is often performed using microfluidic cartridges. Here, the detection of the results is often carried out using fluorescence spectroscopy. Therefore, it is advantageous if the cartridge cover device exhibits no significant autofluorescence in the range of typical excitation and detection wavelengths of common fluorescent dyes. This range extends approximately from 460 to 720 nm.
[0050] In a further embodiment, the cartridge covering device is particularly suitable for adhering to surfaces made of plastics such as COP and PET if their surfaces have previously been energetically enhanced with plasma.
[0051] In a further embodiment, the cartridge covering device is particularly suitable for adhering to surfaces made of metal, glass, ceramic, glass fiber reinforced plastic (GRP), carbon fiber reinforced plastic (CFRP) and / or other higher energy surfaces.
[0052] In a further development, the cartridge covering device has bonding strengths between 6 and 20 MPa, depending on formulation details, radiation dose and substrates to be bonded.
[0053] In a further development, the cartridge covering device is suitable for (semi-)structural bonding of plastics and other low-energy surfaces.
[0054] A second aspect of the invention relates to a method for producing a cartridge cover device according to the first aspect of the invention. The method comprises the following steps: applying the adhesive, which is pressure-sensitive at room temperature, to a carrier material. The adhesive can be applied to a carrier material, for example, using a doctor blade. The carrier material can be, for example, a polyester film. The polyester film advantageously has a thickness of 10-200 µm. The carrier material can also be a temperature- and media-resistant film, alternatively a PET film, a PC film, a COP film, or the like. In a further development, the adhesive can also be solvent-containing. The carrier material can also advantageously have an adhesive-repellent coating, advantageously a silicone layer, on one or both sides.
[0055] Drying the composite. For example, the composite can first be dried for 10 minutes at room temperature and then for 10 minutes at 80°C in a convection oven. The application rate can be adjusted to produce a predetermined layer thickness after drying. Drying can involve removing the solvent mixture. After drying, a pressure-sensitive adhesive or a tacky layered adhesive can be obtained.
[0056] In one embodiment, this adhesive adheres to the carrier material remaining in the product on one side. In another embodiment, the adhesive can also be first coated onto an adhesive-repellent carrier material, such as a siliconized film, and then, after drying, laminated onto the remaining top layer in the product.
[0057] In a further development, a second cover layer can be added to the composite, which advantageously protects the composite.
[0058] In a further development, no protective measures against UV light are required for handling the raw materials, the adhesive, or the coating. Working in a normal laboratory environment away from a UV lamp is sufficient. Additional shielding is not necessary.
[0059] In a further development, stamped parts can be manufactured from the composite.
[0060] A third aspect of the invention relates to a method for producing a system according to the first aspect of the invention. This method comprises the following steps: UV activation of the cartridge cover device. The curing of the adhesive tapes and die-cut parts is activated by UV light, preferably UVA or UVC light. For example, a UV-LED lamp with a wavelength of 365 nm can be used for this purpose. The films used here are normally sterilized by UV light before use. This step can be combined with the activation step to generate further process efficiency.
[0061] Sealing the microfluidic cartridge by joining a second side of the cartridge cover device to the microfluidic cartridge within the open time, or before the expiration of the open time of the layered adhesive. If there is another cover layer on this side of the adhesive, such as a release liner, this should be removed before joining. Joining can be carried out, for example, by placing the cartridge cover device onto the microfluidic cartridge. Light pressure is advantageous in this case. By applying a cover layer of the cartridge cover device on the side facing away from the cartridge, it can be prevented that parts of the adhesive stick to the pressure device, such as a press die.
[0062] If necessary, the top layer applied to a first side of the adhesive can be removed after pressing. Alternatively, the top layer can also be removed after curing. This means there are no or fewer requirements regarding the optical properties, such as autofluorescence or transparency of the top layer.
[0063] Curing the cartridge cover assembly on the microfluidic cartridge. After UV activation, there is a certain period of time during which the parts to be joined can be finally aligned and joined. In a further development, further activation after initiating curing with UV light is no longer necessary.
[0064] Due to the immediate adhesion of the adhesive tape to the cartridge, the sealed cartridge can be transported immediately. During storage, the epoxy resin adhesive can fully cure without any further intervention. The curing reaction takes place in several steps. The duration of the dark reaction can depend on various factors such as the resin component used (cycloaliphatic or aromatic epoxy resin), the chain length, the initiator type, the irradiation time, the irradiation dose (UV wavelength), and even the temperature.
[0065] The curing time after irradiation can be between 0 seconds and 60 minutes, depending on the factors mentioned and their interaction.
[0066] In a further development, the layered adhesive is largely fully cured after a maximum of two hours, so that the adhesive no longer sticks to the channels. Thermosets are known for their high resistance to temperatures and chemicals. For samples that are sensitive to monomers, subsequent storage (e.g., 1 hour at approximately 60°C) can help the remaining monomers to react.
[0067] In a further embodiment, the layered adhesive cures without the introduction of heat.
[0068] In a further embodiment, the layered adhesive cures when heat is applied.
[0069] The layered adhesive can exhibit very high sealing strength, comparable to that of heat-sealing films, but can cure at room temperature and can therefore also be used for temperature-sensitive reagents. Advantageously, the process does not require a heat-sealing station. Alternatively, a heat-sealing station can be used, as a slightly elevated temperature of, for example, approximately 35-45°C can increase the wetting of the layered adhesive on the surface of the microfluidic cartridge.
[0070] In a further embodiment, the layered adhesive cures without additional introduction of UV light.
[0071] In a further preferred embodiment, the UV activation takes place spatially separated from the microfluidic cartridge; alternatively, the UV activation takes place on the microfluidic cartridge, i.e. during or after joining the cartridge covering device to the cartridge.
[0072] In a further embodiment, the UV activation takes place before the cartridge cover device is joined to the microfluidic cartridge, alternatively during or after the cartridge cover device is joined to the microfluidic cartridge.
[0073] Because the adhesive can remain tacky for a certain period of time even after UV activation during the open time, UV activation can also occur before the cartridge cover device is joined to the microfluidic cartridge. This also allows UV activation of the layered adhesive spatially separated from the microfluidic cartridge, for example, outside of a sealing station with the provided microfluidic cartridge. This ensures that UV irradiation has no influence on the functionality of the microfluidic cartridge or on the functionality of the reagents used. In a preferred further development, the cartridge cover device is sterilized by the spatially separated UV activation.
[0074] UV activation of the layered adhesive after assembly can also be beneficial to improve process efficiency. For example, UV activation can also sterilize the microfluidic cartridge, eliminating the need for a separate sterilization step. Short description of the characters
[0075] Preferred further embodiments of the invention are explained in more detail in the following description of the figures. In the figures: Figure 1 schematically a cartridge covering device 10 comprising a first cover layer 50; Figure 2 schematically the cartridge covering device 10 from Figure 1 , which comprises an additional second cover layer 51; Figure 3 schematically a cartridge covering device 10 comprising a release liner; Figure 4 schematically a cartridge covering device 10 which comprises a release film on both sides; Figure 5schematically a cartridge cover device 10 which seals a microfluidic cartridge 20; and Figure 6 schematically a layered adhesive 30 which comprises filler 40. Detailed description of preferred embodiments
[0076] Preferred embodiments are described below with reference to the figures. Identical, similar, or equivalent elements in the different figures are provided with identical reference numerals, and a repeated description of these elements is partially omitted to avoid redundancies.
[0077] In Figure 1 An embodiment of the cartridge covering device 10 is shown schematically, which comprises a layered adhesive 30. The composition of the layered adhesive 30 is determined by the following ranges: i. 2-40 wt.% film formers, ii. 10-70 wt.% aromatic epoxy resins, iii. cycloaliphatic epoxy resins, whereby the cycloaliphatic epoxy resins do not exceed 35 wt.%, iv. 0.5-7 wt.% cationic initiators, v. 0-50 wt.% epoxidized polyether compounds, and vi. 0-20 wt.% polyol, where the shares add up to 100%.
[0078] In the present embodiment, the layered adhesive 30 comprises: i. 11 wt.% film formers, ii. 58 wt.% aromatic epoxy resins, iii. 10 wt.% cycloaliphatic epoxy resins, iv. 2 wt.% cationic initiators, v. 12 wt.% epoxidized polyether compounds, and vi. 7 wt.% polyol
[0079] The following are examples of specific product names of the individual components of the layered adhesive 30: i. 11 wt.% film formers, in particular Desmomelt 530, ii. 58 wt.% aromatic epoxy resins, in particular 38% Araldite GT 7072 and 20% DER 331, iii. 10 wt.% cycloaliphatic epoxy resins, in particular Uvacure 1534, iv. 2 wt.% cationic initiators, in particular Chivacure 1176, v. 12 wt.% epoxidized polyether compounds, in particular DER 736 P, and vi. 7 wt.% polyol, in particular PEG 400.
[0080] In the Figure 1 In the cartridge cover device shown, the thickness of the layered adhesive is 30-70 µm. Alternatively, the thickness can be 2 to 1000 µm, preferably 5 to 500 µm, and particularly preferably 5 to 100 µm. The first side of the layered adhesive 32 and the second side of the layered adhesive 34 are also shown schematically.
[0081] A cover layer 50 in the form of a polyester film carrier is arranged on the first side 32 of the layered adhesive 30. However, any other cover layer, preferably a plastic film, can also be used as the cover layer. Advantageously, the cover layer 50 can also be a temperature- and media-resistant film, preferably a PET film, a PC film, a COP film, or the like.
[0082] The cover layer 50 in this embodiment has a thickness of 100 µm, but it can also have a different thickness, in particular a thickness of 10-200 µm. The cover layer 50 in this embodiment has a silicone coating on the side 54 facing away from the layered adhesive 30. Alternatively, any other adhesive-repellent coating, in particular a silicone system, could also be provided.
[0083] The adhesive-repellent coating is advantageously selected to exhibit sufficiently high adhesion to the epoxy resin system. This is advantageous in that it allows the cartridge cover device 10 to be wrapped in itself, for example, for storage.
[0084] The cover layer 50 is preferably selected such that the autofluorescence does not lie in the wavelength range used by common fluorescent dyes. This is not the case in this embodiment, since the autofluorescence of the adhesive and cover layer lies in the range of 230-450 nm.
[0085] The polyester film carrier 50 in this embodiment has no further coating on the side 52 facing the layered adhesive 30. This is advantageous in this embodiment because the cover layer 50 is intended to remain on the layered adhesive 30. The cover layer 50 can thus serve, for example, as a one-sided protective film for the layered adhesive 30 of the cartridge cover device 10.
[0086] The layered adhesive 30 is UV-activated to initiate curing and is tacky before and after activation until the end of an open time at room temperature.
[0087] In Figure 2 A cartridge covering device 10 is shown schematically, which essentially corresponds to the Figure 1 shown cartridge cover device 10. The Figure 2 The cartridge cover device 10 shown differs from the one shown in Figure 1shown cartridge cover device.
[0088] In this embodiment, an additional cover layer 51 in the form of a PET film is arranged on the second side 34 of the layered adhesive 30. Alternatively, any other desired cover layer can also be arranged, preferably in the form of a release film. The cover layer 51 in this embodiment has a thickness of 50 µm, but it can also have a different thickness, in particular a thickness of 2 to 1000 µm, preferably of 5 to 500 µm, and particularly preferably of 5 to 100 µm.
[0089] The cover layer 51 has a silicone coating on the side 53 facing the layered adhesive 30, but it could also have any other adhesive-repellent surface. The adhesive-repellent coating is advantageously selected to exhibit sufficiently high adhesion to the epoxy resin system. This may be necessary so that the PET film can be removed before joining it to the microfluidic cartridge. This gives the cover layer 51 the function of a release liner.
[0090] Furthermore, the cover layer 51 has a silicone coating on the side 55 facing away from the layered adhesive 30. Alternatively, the cover layer can also have any other adhesive-repellent surface. The silicone coating on the side 55 facing away from the layered adhesive 30 serves storage purposes and, for example, facilitates the rolling up and unrolling of the cartridge cover device 10 if the latter is to be stored in roll form.
[0091] In Figure 3 a cartridge covering device 10 is shown schematically, which comprises a layered adhesive 30, which corresponds to the adhesive from Figure 1 corresponds.
[0092] The cartridge cover device according to Figure 3 has a cover layer 51 in the form of a PET film only on the second side 34 of the layered adhesive 30. Structure and properties of the Figure 3The cover layer 51 shown corresponds to those of the second cover layer of Figure 2 Since the cover layer 51 does not remain in the product, there are no requirements for autofluorescence properties.
[0093] In Figure 4 An embodiment of the cartridge covering device 10 is shown schematically, which essentially corresponds to the cartridge covering device of Figure 1 corresponds.
[0094] The Figure 4 The cartridge cover device shown differs from the cartridge cover device according to Figure 1 that the cover layer 50 in the form of a PET film has a silicone coating on the side 52 facing the layered adhesive 30. Alternatively, the cover layer 50 can also have any other adhesive-repellent surface.
[0095] The adhesive-repellent coating is advantageously selected so that it has sufficiently high dehesion, i.e., it can be removed manually or mechanically without significant force, without external damage and without negatively impairing the functional properties of the adhesive surface of the epoxy resin system. This may be necessary so that the cover layer 50 can be removed before joining it to the microfluidic cartridge. The cover layer 50 also has a silicone coating on the side 54 facing away from the layered adhesive 30. This coating can also alternatively be any other adhesive-repellent surface.
[0096] Thus, the cartridge covering device 10 according to Figure 4 A removable cover layer 50, 51 is applied to both sides of the adhesive 30. A double release liner can be particularly helpful when very high quality demands are placed on the product's appearance.
[0097] In Figure 5 A cartridge cover device 10 is shown schematically, which is assembled with a microfluidic cartridge 20. The cartridge 20 has recesses on its upper surface, such as cavities, chambers, channels, and the like, which serve to accommodate reagents, such as those of an in-vitro assay, in order to perform in-vitro diagnostics. The cartridge cover device 10 is arranged on the cartridge 20 in such a way that the recesses in the surface of the cartridge 20 are sealed from the environment.
[0098] In Figure 6A layered adhesive 30 is schematically shown, which comprises filler bodies 40 in the form of solid glass spheres. The maximum dimension of the filler bodies 40 is smaller than the thickness of the layered adhesive 30. The filler bodies 40 have, among other things, a beneficial effect on the elastic properties of the layered adhesive and on the elastic properties of the cartridge cover device, which in turn leads to a beneficial sealing of the microfluidic cartridge.
[0099] The layered adhesive 30 can alternatively also comprise other fillers 40, such as hollow glass spheres and / or polymer spheres. However, fillers 40 made of other materials can also be used, in particular ceramic or polymer-based fillers. The first side of the layered adhesive 32 and the second side of the layered adhesive 34 are also shown schematically.
[0100] The following are the desired requirements for the material (silicone layer, carrier, adhesive system) for use in in vitro diagnostics.
[0101] Cyclic heating and cooling is required for pathogen DNA replication. For this, the reagents are heated to approximately 95°C for 30 seconds in approximately 50–100 cycles and then cooled back to approximately 60°C. The film material and seal must withstand these temperature cycles. Temperature resistance of the seal at ≥ 90°C for approximately 50–100 cycles for 20 seconds is advantageous. The results are detected using fluorescence spectroscopy. An optically transparent seal (transmission > 90%) is advantageous for detection. The following wavelengths are used for detection and should be able to pass through the material unchanged: Green: Excitation: 470 ± 10 nm; Detection: 510 ± 0.5 nm Yellow: Excitation: 530 ± 0.5 nm; Detection: 557 ± 0.5 nm Orange: Excitation: 585 ± 0.5 nm; Detection: 610 ± 0.5 nm Red: Excitation: 625 ± 0.5 nm; Detection: 660 ± 10 nm Crimson: Excitation: 680 ± 0.5 nm; Detection: 712 ± 0.5 nm
[0102] Since the results are detected using fluorescence spectroscopy, the material should also exhibit no fluorescence in the detection wavelength range. The seal strength should withstand a pressure of 1 bar (equivalent to 0.1 N / mm²) at 100°C.
[0103] The sealing layer in contact with the product should not contain any ingredients that affect the biochemistry of the sample material or reagents.
[0104] Various alcoholic solvents are used during the process. Therefore, chemical stability against solvents such as ethanol or isopropanol (diluted solutions; 50%) is advantageous.
[0105] The material should not show any brittleness and should be flexible (not bendable) after production. It should also not break during disposal after use, so that no substances such as reagents or blood containing pathogens can leak out.
[0106] During processing of the film, no toxic substances should escape that could have a harmful effect on the health of the operating personnel.
[0107] The material should exhibit only low water absorption (< 10%) within the 2-hour processing time. The lower the water absorption capacity, the lower the risk of pathogens adhering to or sticking to the material or of material properties changing.
[0108] To ensure an appropriate processing time, the sealing film should adhere sufficiently to the microfluidic cartridge after 20 seconds, allowing it to be packaged. Complete curing can occur during storage.
[0109] Another optical requirement for the adhesive is that no bubbles should form when the adhesive cures.
[0110] The microfluidic cartridge is covered in a clean room, which usually has a low humidity of approximately 35-50% rH. List of reference symbols
[0111] 10Cartridge cover device 20Microfluidic cartridge 30Layered adhesive 32First side of the layered adhesive 34Second side of the layered adhesive 40Filling body 50Cover layer 51Cover layer 52Side of the cover layer facing the layered adhesive 53Side of the cover layer facing the layered adhesive 54Side of the cover layer facing away from the layered adhesive 55Side of the cover layer facing away from the layered adhesive
Claims
1. A system comprising a microfluidic cartridge (20) and a cartridge covering element (10) for sealing off the microfluidic cartridge (20), the cartridge covering element (10) comprising: at least one stratified adhesive mass (30) characterized in that the stratified adhesive mass (30) is adapted to be UV-activatable to induce curing and adapted to be tacky after activation until expiration of an open time at room temperature, wherein the stratified adhesive mass (30) comprises: i. 2 - 40 percent by weight of film former, ii. 10 - 70 percent by weight of aromatic epoxy resins, iii. cyclo-aliphatic epoxy resins, the cyclo-aliphatic resins not exceeding 35 percent by weight, iv. 0,5 - 7 percent by weight of cationic initiators, v. 0 - 50 percent by weight of epoxy-enhanced polyether compounds, and vi. 0 - 20 percent by weight of polyol, such that shares of the components by weight add up to 100 %.
2. System according to claim 1, characterized in that the stratified adhesive mass (30) has a thickness of 2 to 1.000 pm, preferably 5 to 500 pm and especially preferably 5 to100 pm.
3. System according to any of the preceding claims, characterized in that the stratified adhesive mass (30) comprises fillers (40), in particular ceramic fillers or polymer-based fillers.
4. System according to claim 3, characterized in that the fillers (40) are solid glass spheres, hollow glass spheres and / or polymer spheres.
5. System according to claim 3 or 4, characterized in that the maximum dimensions of a filler (40) are smaller than the thickness of the stratified adhesive mass (30).
6. System according to any of the preceding claims, characterized in that a cover layer (50), preferably a plastic foil, is arranged on a first side (32) of the stratified adhesive mass (30).
7. System according to any of the preceding claims, characterized in that a cover layer (51), in particular a release liner, is arranged on a second side (34) of the stratified adhesive mass (30).
8. System according to claim 6 or 7, characterized in that the cover layer (50, 51) has an adhesive-repellent coating on a side (52, 53) facing the stratified adhesive mass (30) and / or on a side (54, 55) facing away from the stratified adhesive mass (30).
9. System according to one of the claims 6 to 8, characterized in that the cover layer (50, 51) is a temperature- and media-resistant film, preferably a PET foil, a PC foil or a COP foil.
10. A method for manufacturing a system according to one of the claims 1 to 9, comprising the following steps: UV-activation of the cartridge covering element (10), sealing off the microfluidic cartridge (20) by joining a second side of the cartridge covering element (10) and the microfluidic cartridge within the open time of the stratified adhesive mass (30), and curing the cartridge covering element (10) on the microfluidic cartridge (20).
11. Method according to claim 10, characterized in that the UV-activation takes place spatially separated from the microfluidic cartridge (20).
12. Method according to claim 10 or 11, characterized in that the UV-activation takes place prior or during the joining of the cartridge covering element (10) and the microfluidic cartridge (20).