Microfluidic cartridge and methods for its disassembly

Abstract

The invention relates to a microfluidic cartridge (10) comprising an array chamber (14) in which an array (15) is bonded by means of an adhesive (16). The adhesive (16) contains at least one additive component which undergoes a chemical reaction with the adhesive (16) under the influence of microwaves, resulting in at least partial degradation of the adhesive (16). In a method for disassembling the microfluidic cartridge (10), the adhesive (16) is at least partially degraded by microwave irradiation, and the array (15) is subsequently removed from the array chamber (14).

Description

[0001] The present invention relates to a microfluidic cartridge. The present invention also relates to a method for disassembling the microfluidic cartridge. State of the art

[0002] Microfluidic cartridges are manufactured from various plastic components and used for the analysis of bodily fluids and for timely diagnostics in medical practices and hospitals. These cartridges feature an array chamber in which the bodily fluid is combined with various reagents and analyzed using an optical unit of an analysis system into which the microfluidic cartridge is inserted. For this purpose, the array chamber contains an array with multiple cavities, each holding a different reagent. The array can be bonded to the array chamber using, for example, a UV-curing adhesive, as described in WO 2014 / 023661 A2.

[0003] After the patient sample in the cartridge has been analyzed, the cartridge is disposed of. This process destroys costly manufactured components and materials. Disclosure of the invention

[0004] The microfluidic cartridge has an array chamber in which an array is bonded using an adhesive. The array is made of silicon. It features microcavities with a diameter preferably in the range of 10 µm to 1,000 µm and particularly preferably in the range of 100 µm to 400 µm. This ensures, on the one hand, that filling the microcavities with a patient sample is straightforward and, on the other hand, that a sufficiently large number of microcavities can be arranged on the array. The depth of the microcavities is preferably in the range of 100 µm to 700 µm, particularly preferably in the range of 200 µm to 300 µm. This ensures sufficient capacity of the cavities and, on the other hand, prevents excessive material removal from the array. Reagents are pre-filled in the microcavities.

[0005] The adhesive contains at least one additive component designed to undergo a chemical reaction with the adhesive, i.e., with the remaining adhesive or components of the adhesive, when exposed to microwaves. This chemical reaction results in at least partial degradation of the adhesive. While an array is conventionally irreversibly bonded to at least one wall of the array chamber, the bonding method presented here allows the connection between the array and the array chamber to be broken after use of the microfluidic cartridge by exposure to microwaves, so that at least the array and, if necessary, other components of the microfluidic cartridge can be recycled.

[0006] Partial degradation of the adhesive means that polymer chains within the adhesive are broken, and the adhesive is softened or liquefied due to chain shortening.

[0007] It has been found that epoxy resins, especially those containing an additive component, can be at least partially degraded. Therefore, such an adhesive or its copolymer is preferably used.

[0008] Furthermore, it is preferred that the adhesive contains a photoinitiator. This allows the adhesive to be cured by photopolymerization. This avoids the thermal induction of the microwave-induced chemical reaction of the additive component with the adhesive, which would otherwise be necessary for thermal polymerization.

[0009] Particularly preferred is a photoinitiator that enables photopolymerization by exposure to light with a wavelength in the range of 320 nm to 450 nm.

[0010] The adhesive, in its unpolymerized state, is preferably a mass consisting of the following components: A 30 to 60 wt.%, particularly preferably 40 to 60 wt.%, most preferably 45 to 60 wt.%, of an at least bifunctional epoxy-containing compound, B 5 to 35 wt.%, particularly preferably 10 to 30 wt.%, most preferably 15 to 35 wt.%, of a hybrid compound comprising at least one isocyanate group and at the same time at least one radically polymerizable group, wherein the radically polymerizable group is selected in particular from the group of acrylates or methacrylates. C 5 to 40 wt.%, particularly preferably 20 to 40 wt.%, most preferably 25 to 40 wt.%, of a latent hardener based on nitrogen compounds suitable for addition crosslinking of the epoxy-containing compound, wherein the latent hardener has a number-average particle size of particularly at most 10 µm, and D 0.2 to 5.0 wt.% of a photoinitiator capable of radical formation upon irradiation with light, where components A to D together constitute 100 wt.%.

[0011] Component A can be aliphatic, cycloaliphatic and aromatic epoxy resins, as well as mixtures thereof.

[0012] Aliphatic epoxy resins contain components that bear both an aliphatic group and at least two epoxy groups. Examples of components of aliphatic epoxy resins include, in particular, butanediol diglycidyl ether, hexanediol diglycidyl ether, dimethyl pentane dioxide, butadiene dioxide, and diethylene glycol diglycidyl ether. Cycloaliphatic epoxy resins contain components that bear both a cycloaliphatic group and at least two oxirane rings. Examples include 3-cyclohexenylmethyl-3-cyclohexylcarboxylate diepoxide, 3,4-epoxycyclohexylalkyl-3',4'-epoxycyclohexanecarboxylate, 3,4-epoxy-6-methylcyclohexylmethyl-3',4'-epoxy-6-methylcyclohexanecarboxylate, vinylcyclohexane dioxide, bis(3,4-epoxycyclohexylmethyl)adipate, dicyclopentadiene dioxide, and 1,2-epoxy-6-(2,3-epoxypropoxy)hexahydro-4,7-methanindane. 3,4-Epoxycyclohexylmethyl-3',4'-epoxycyclohexylcarboxylate is preferred. Aromatic epoxy resins can also be used.Examples of aromatic epoxy resins include bisphenol-A epoxy resins, bisphenol-F epoxy resins, phenol-novolac epoxy resins, cresol-novolac epoxy resins, biphenyl epoxy resins, 4,4'-biphenyl epoxy resins, divinylbenzene dioxide, and 2-glycidylphenyl glycidyl ether. Furthermore, polyfunctional epoxy resins from all three resin groups, toughened epoxy resins, and mixtures of different epoxy resins can also be used.

[0013] The hybrid compounds used as component B, comprising at least one free isocyanate group and at least one radically radiation-curing group, can be obtained by partially reacting the isocyanate groups of a molecule bearing at least two isocyanate groups with a compound containing at least one radically radiation-curing group and one hydroxyl group. Depending on the number of isocyanate groups initially present, a different number of radically radiation-curing groups can be introduced into the hybrid compound. For example, in a molecule with four isocyanate groups, one, two, or three of these groups can be selectively converted into radically radiation-curing groups. Compounds of the formula Q(NCO) are preferably used as polyfunctional isocyanates for the synthesis of the hybrid compound. nin question, wherein n = 2 to 5, preferably 2 or 4, and Q represents an aliphatic hydrocarbon residue with 2-18, preferably 6-10 C atoms, a cycloaliphatic hydrocarbon residue with 4-15, preferably 5-10 C atoms, or an aromatic hydrocarbon residue with 6-15, preferably 6-13 C atoms.Examples of isocyanates of the above-mentioned general formula with multiple isocyanate groups are low-molecular-weight isocyanates such as hexamethylene diisocyanate, 1,12-didecane diisocyanate, cyclobutane-1,3-diisocyanate, cyclohexane-1,3- and -1,4-diisocyanate and any mixtures of these isomers, 1-isocyanato-3,3,5-trimethyl-5-isocyanatomethylcyclohexane, hexahydro-1,3- and / or-1,4-phenylene diisocyanate, perhydro-2,4'- and / or -4,4'-diphenylmethane diisocyanate, 1,3- and 1,4-phenylene diisocyanate, 2,4- and 2,6-toluene diisocyanate and any mixtures of these isomers, diphenylmethane-2,4'- and / or -4,4'-diisocyanate, naphthylene-1,5-diisocyanate, triphenylmethane-4,4',4"-triisocyanate, or Polyphenyl-polymethylpolymethylene polyisocyanates, as obtained by aniline-formaldehyde condensation and subsequent phosgenation.Higher molecular weight isocyanates, i.e., polyfunctional isocyanates with, in particular, isocyanurate, carbodiimide, allophanate, biuret, or uretdione structural units, are preferably synthesized from these low molecular weight isocyanates. Preferred higher molecular weight isocyanates are, in particular, prepolymers with terminal isocyanate groups and a molecular weight in the range of 400 to 10,000, preferably 600 to 8,000, and especially 800 to 5,000. These higher molecular weight isocyanates are obtained by reacting excess amounts of the aforementioned low molecular weight isocyanates with organic compounds containing at least two groups reactive towards isocyanate groups, such as organic polyhydroxy compounds.

[0014] Component C is defined as any hardener that remains inactive under storage conditions for a certain period but becomes active upon heating to a temperature between approximately 60 and 160°C, triggering a polyaddition and crosslinking reaction between the hardener and the epoxy resin. Examples of latent hardeners include, in particular, dicyandiamide, guanidine derivatives, triazine derivatives, guanine derivatives, aliphatic amines, cycloaliphatic amines, aromatic amines, polyamidoamines, and imidazoles. Further examples of latent hardeners are all polymeric nitrogen-containing compounds, provided an addition reaction with epoxy resins is possible. Adducts of epoxy resins with various amines are particularly preferred.

[0015] Component D may in particular be compounds selected from the group consisting of α-hydroxyketones, benzophenone, α,α-diethoxyacetophenone, 4,4-diethylaminobenzophenone, 2,2-dimethoxy-2-phenylacetophenone, 4-isopropylphenyl-2-hydroxy-2-propylketone, 1-hydroxycyclohexylphenylketone, isoamyl-p-dimethylaminobenzoate, methyl-4-dimethylaminobenzoate, methyllobenzoylbenzoate, benzoin, benzoin ethyl ether, benzoin isopropyl ether, benzoin isobutyl ether, 2-hydroxy-2-methyl-1-phenylpropan-1-one, 2-isopropylthioxanthone, dibenzosuberone, 2,4,6-trimethylbenzoyldiphenylphosphine oxide, bisacylphosphine oxides and mixtures thereof.

[0016] The mass may also contain 0 to 80 wt.%, based on the total weight of components A to D, modifiers selected from the group consisting of fillers, dyes, pigments, stabilizers, humectants, accelerators, flow improvers, wetting agents, thixotropic agents, thinners, polymeric thickeners and mixtures thereof.

[0017] The additive component preferably comprises or consists of an organic amine, for example octylamine, or an organic acid. These additive components cause a base-catalyzed or acid-catalyzed cleavage of the epoxy backbone of the adhesive.

[0018] The organic acid is specifically selected from the group consisting of acetic acid, formic acid, trifluoroacetic acid, oxalic acid, benzenesulfonic acid and 4-dodecylbenzenesulfonic acid.

[0019] To enable sufficient degradation of the adhesive by exposure to microwaves on the one hand, and to avoid unnecessary influence of the additive component on the other hand, the adhesive preferably contains 1 wt.% to 10 wt.%, particularly preferably 1 wt.% to 5 wt.% of the additive component, based on 100 wt.% of the adhesive.

[0020] An interaction of the additive component with the components of the adhesive during its polymerization can be further preferably prevented by enclosing the additive component in capsules. These capsules preferably contain or consist of an amino resin. Such an amino resin does not react with the components of the adhesive during photoinitiated polymerization, but dissolves under the influence of microwaves, allowing the additive component to react with the polymerized adhesive. The diameter of the capsules is particularly in the range of 1 µm to 100 µm.

[0021] The microfluidic cartridge comprises, in particular, a fluidic layer and a pneumatic layer, between which an elastomeric membrane is arranged. The fluidic layer is defined as a layer containing chambers and channels in which a patient sample can be transported and reacted with reagents. These reagents, as well as solvents, may be located upstream of the fluidic layer in chambers and / or reagent bars. At least one of the channels and / or one of the chambers borders the elastomeric membrane. The pneumatic layer has channels that also border the elastomeric membrane at one end and are configured at the other end to be connected to a pneumatic manifold of an analytical device. The pneumatic manifold can be used to generate positive or negative pressure in the channels of the pneumatic layer.In this way, the elastomer membrane is deflected into the pneumatic or fluidic layer, allowing the manipulation of fluids in the chambers and channels of the fluidic layer. The array chamber is located at least partially within the fluidic layer but can also extend partially into the pneumatic layer. It features a window, particularly on its side facing away from the elastomer membrane, which enables the spectroscopic investigation of chemical reactions in the array's microcavities using an analytical device. The fluidic and pneumatic layers are each welded to the elastomer membrane. This weld is typically produced by laser welding during the fabrication of the microfluidic cartridge.

[0022] The fluidic layer and the pneumatic layer are preferably each made of polycarbonate. Polycarbonates are transparent and therefore have the advantage that laser welding of the microfluidic cartridge components through the polycarbonate is possible. A window for the array chamber can also be machined into the polycarbonate without having to insert a window made of a separate material. For the present cartridge design, however, the use of polycarbonate has the additional advantages that it bonds well with adhesives and that UV curing of the adhesive can take place through the transparent polycarbonate.

[0023] The elastomer membrane consists primarily of thermoplastic polyurethane, which is elastic on the one hand and can be easily welded to the polycarbonate of the fluidic layer and the pneumatic layer by means of laser welding.

[0024] After the microfluidic cartridge has been used in an analyzer, the disassembly procedure involves heating the adhesive by microwave irradiation, at least partially breaking it down and causing it to soften or liquefy. The array can then be removed from the array chamber for reuse after cleaning away any remaining adhesive residue and reagents from the patient sample.

[0025] If the microfluidic cartridge consists of a fluidic layer, a pneumatic layer, and an elastomer membrane, then microwave treatment of the entire cartridge also advantageously breaks the weld between the fluidic layer and the elastomer membrane, as well as between the pneumatic layer and the elastomer membrane. In this case, it is preferred that these components are first separated from each other before the array is removed from the array chamber, as this provides easy access. Furthermore, the non-destructive separation of the components allows the fluidic layer and the pneumatic layer to be reused, after cleaning, to manufacture a new microfluidic cartridge. Brief description of the drawings

[0026] Exemplary embodiments of the invention are shown in the drawings and are explained in more detail in the following description. Fig. Figure 1 shows a schematic cross-sectional view of a microfluidic cartridge according to an embodiment of the invention. Fig. Figure 2 shows a flowchart of a method according to an embodiment of the invention. Exemplary embodiments of the invention

[0027] Fig. Figure 1 schematically shows a microfluidic cartridge 10 according to an embodiment of the invention. This cartridge has a fluidic layer 11 made of polycarbonate, in which chambers and channels are formed. It also has a pneumatic layer 12 with pneumatic channels. This pneumatic layer is also made of polycarbonate. An elastomeric membrane 13 made of thermoplastic polyurethane is arranged between the fluidic layer 11 and the pneumatic layer 12. This membrane was welded to the fluidic layer 11 and the pneumatic layer 12 by laser welding, with the welding laser beam being directed through the transparent material of the fluidic layer 11 and the pneumatic layer 12. An array chamber 14 extends through the fluidic layer 11 and the pneumatic layer 12. The elastomeric membrane 13 is perforated in the region of the array chamber 14. The array chamber 14 is in fluidic communication with the channels and chambers of the fluidic layer 11.In its section located in the pneumatic layer 12, an array 15 is bonded into the array chamber 14 by means of an adhesive 16. The array 15 consists of silicon and has microcavities in which different reagents are pre-positioned. The adhesive 16 was obtained by mixing and homogenizing the following components:

[0028] 515 g bisphenol-A epoxy resin (Araldite GY 250 from Huntsman), 203 g hybrid compound (Laromer LR 9000 from BASF), 260 g latent hardener (EH-4360S from ADEKA), 13 g photoinitiator (CGI 403 from BASF), 12 g thixotropic agent (HDK H18 from WACKER), 40 g amino resin encapsulated octylamine.

[0029] The adhesive 16 is cured by first irradiating it through the transparent polycarbonate with ultraviolet light in a wavelength range of 320 nm to 450 nm and then heating it to a temperature of 80°C.

[0030] Fig. Figure 2 shows in a flowchart the process steps that are carried out with the microfluidic cartridge 10 over its lifetime. After the start 20 of the manufacturing process, the array 15 is first inserted 21 into the array chamber 14, whereby its contact surfaces with the polycarbonate of the pneumatic layer 12 are wetted with the adhesive 16. The adhesive 16 is then cured 22 by irradiation and subsequent heating. Afterward, the fluidic layer 11, the pneumatic layer 12, and the elastomer membrane 13 are assembled into the Fig. The structure of the microfluidic cartridge 10 shown in 1 is assembled 23, and welded together using a laser 24.

[0031] The microfluidic cartridge 10 produced in this way is then passed on to a doctor's office or hospital. There, it is filled with a patient sample 31 and subsequently inserted into an analyzer 32. In the analyzer, the patient sample is first pretreated with reagents located upstream in the fluid layer 11 and then directed into the array chamber 14 to distribute it among the cavities in the array 15 and react with the reagents located upstream therein. The results of the chemical reactions are evaluated using an optical detection device of the analyzer 33. Subsequently, the used microfluidic cartridge 10 is removed from the analyzer 34.

[0032] Unlike a conventional microfluidic cartridge, the microfluidic cartridge 10 according to the invention is not disposed of. Instead, it is returned to the manufacturer and subjected to microwave treatment 41. The heating of the microfluidic cartridge 10 caused by the microwave treatment loosens the welded connection between the elastomer membrane 13 and the fluidic layer 11 and the pneumatic layer 12, allowing these components to be separated 42. Furthermore, the amino resin capsules melt under the influence of the microwaves and release the octylamine. The microwave treatment provides sufficient activation energy for the octylamine to undergo a base-catalyzed cleavage of the epoxy backbone of the polymerized adhesive 16, thus softening it. The array 15 can then be removed from the array chamber 14 43 and cleaned of any remaining adhesive 16.At the end of step 44 of the process, the fluidic layer 11, the pneumatic layer 12 and the array 15 are again available as individual components, which can be reassembled into a microfluidic cartridge 10 after thorough cleaning. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] WO 2014 / 023661 A2

[0002]

Claims

[1] Microfluidic cartridge (10) comprising an array chamber (14) in which an array (15) is glued by means of an adhesive (16), characterized by that the adhesive (16) contains at least one additional component which is designed to undergo a chemical reaction with the adhesive (16) under the influence of microwaves, in which at least partial degradation of the adhesive (16) takes place. [2] Microfluidic cartridge (10) according to claim 1, characterized by that the adhesive (16) comprises or is an epoxy resin or its copolymer. [3] Microfluidic cartridge (10) according to claim 2, characterized by , that the adhesive (10) contains a photoinitiator. [4] Microfluidic cartridge (10) according to any one of claims 1 to 3, characterized by that the additive component contains or is an organic amine or an organic acid. [5] Microfluidic cartridge (10) according to any one of claims 1 to 4, characterized bythat the additional component is enclosed in capsules. [6] Microfluidic cartridge (10) according to claim 5, characterized by that the capsules contain or consist of an amino resin. [7] Microfluidic cartridge (10) according to any one of claims 1 to 6, characterized by , that it has a fluidic layer (11) and a pneumatic layer (12) between which an elastomeric membrane (13) is arranged, wherein the fluidic layer (11) and the pneumatic layer (12) are each welded to the elastomeric membrane (13). [8] Microfluidic cartridge according to claim 7, characterized by that the fluidic layer (11) and the pneumatic layer (12) each contain or consist of a polycarbonate. [9] Method for disassembling a microfluidic cartridge (10) according to any one of claims 1 to 8, wherein the adhesive (16) is at least partially degraded by irradiation (41) with microwaves and the array (15) is subsequently removed from the array chamber (14) (43). [10] Method according to claim 9, characterized by , that the microfluidic cartridge (10) is a microfluidic cartridge (10) according to claim 7 or 8, wherein the irradiation (41) also dissolves the weld connection and separates the fluidic layer (11), the pneumatic layer (12) and the elastomeric membrane (13) from each other (42) before the array (15) is removed from the array chamber (14) (43).

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