Method for manufacturing a microfluidic device

Abstract

The invention relates to a method for manufacturing a microfluidic device (D1, D2), said microfluidic device comprising a first part and a second part to be applied against each other, the first part and the second part each comprising a so-called upper face and a so-called lower face, the method consisting of: - Depositing a first layer (30) of parylene on the upper face of the first part, - Depositing a second layer (40) of parylene on the lower face of the second part, - Applying the first part against the second part so that the first layer of parylene is in contact with the second layer of parylene, - Performing a thermal sealing of the two parts against each other.

Description

Technical field of the invention

[0001] The present invention relates to a method of manufacturing a microfluidic device and to the microfluidic device obtained by this method. State of the art

[0002] Currently, a microfluidic card or cartridge can be manufactured by superimposing several layers. Some of these layers are machined to create the microfluidic circuit of the card. The assembly of the layers together is often carried out by thermal sealing or by gluing, for example using an epoxy or acrylic glue. It is also known to position a microfluidic component on one side of a microfluidic card, to add an additional function to the card. This component is fixed by gluing using an epoxy or acrylic glue or by using double-sided adhesive.

[0003] Solutions for assembling two parts of a microfluidic device are not necessarily satisfactory for several reasons: The glues used must be applied precisely so as not to obstruct the microfluidic network; The glues used can generate risks of pollution in the samples analyzed; The use of double-sided adhesive does not always allow perfect sealing between the different parts of the device;

[0004] Patent application KR2018-0085202 describes a method of manufacturing a chip in which the assembly of two layers is carried out using a layer of parylene and a layer of silicon nitride.

[0005] This previous solution is however not entirely satisfactory because it requires the use of silicon nitride and we want to avoid any pollution of a sample present in the microfluidic network.

[0006] The aim of the invention is to propose a suitable method for assembling two parts of a microfluidic device, which does away with the use of glue, double-sided adhesive and any layer likely to pollute a sample present in the microfluidic network of the device, thus making it possible to resolve the problems of the state of the art. Statement of the invention

[0007] This aim is achieved by a method of manufacturing a microfluidic device, said microfluidic device comprising a first part and a second part to be applied against each other, the first part and the second part each comprising a so-called upper face and a so-called lower face, the method consisting of: Place a first layer of parylene on the upper face of the first part, Place a second layer of parylene on the lower face of the second part, Apply the first part against the second part so that the first layer of parylene is in contact with the second layer of parylene, Heat seal the two parts against each other.

[0008] The solution of the invention uses nothing other than two layers of parylene to allow assembly by thermal sealing. However, it is known that parylene is a biocompatible film, which is not likely to contaminate a sample present in the microfluidic network of the device.

[0009] According to a particularity, the thermal sealing is implemented at a temperature between 110°C and 125°C.

[0010] According to another feature, the heat sealing is carried out by holding the first part against the second part by applying a force between 500N and 1500N.

[0011] According to another feature, the thermal sealing is implemented for a duration of between 5 minutes and 15 minutes.

[0012] The invention also relates to a microfluidic device comprising at least a first part and a second part, assembled with each other, this assembly being obtained by the method as defined above.

[0013] According to a first particular embodiment, the first part is formed from a first layer of a microfluidic card and the second part is formed from a second layer of the microfluidic card to be deposited on the first layer.

[0014] According to a second particular embodiment, the first part is formed of at least a first layer of a microfluidic card and the second part is formed of a deformable membrane which is applied by a first face against a face opposite said first layer.

[0015] According to a feature of this second embodiment, the microfluidic card comprises a second layer and the membrane is interposed between the first layer and the second layer of the microfluidic card, the membrane comprising a second face comprising another layer of parylene adhering to a layer of parylene deposited on a face opposite the second layer.

[0016] According to a third particular embodiment, the first part is formed of a microfluidic card and the second part is formed of a microfluidic component assembled on the card.

[0017] According to a feature of this third embodiment, the microfluidic card comprises a first microfluidic network and the microfluidic component comprises a second microfluidic network, the microfluidic component being assembled on the microfluidic card by establishing a sealed fluidic connection between the first microfluidic network and the second microfluidic network.

[0018] The method of the invention thus makes it possible to assemble several elements made from materials such as COC, COP, PDMS, PMMA, silicon, using low deposits of parylene on the elements to be assembled. Brief description of the figures

[0019] Other characteristics and advantages will appear in the detailed description which follows, given with reference to the attached drawings in which: THE Figures 1A to 1C show several examples of microfluidic devices that can be obtained by the method of the invention; The figure 2 shows the steps of the method of the invention; Detailed description of at least one embodiment

[0020] For the remainder of the description, we define an orthonormal X, Y, Z coordinate system, the Z axis being oriented in the vertical direction. The terms "upper", "lower", "above" and "below" or equivalent are to be understood along the Z axis. Microfluidic device

[0021] In reference to the Figure 1A , in a non-limiting manner, a microfluidic device D1 can for example take the form of a microfluidic card, the two parts of the microfluidic device, described below, being formed of at least two superimposed layers 1, 2 of the microfluidic card, called lower layer 1 and upper layer 2.

[0022] In reference to the Figure 1B, the microfluidic device D2 can also take the form of a multi-layer microfluidic card (at least two layers), one of the layers being a deformable membrane 5, for example made of a hyperelastic silicone-based material, such as polydimethylsiloxane (PDMS), or elastomer such as Ecoflex (registered trademark). The membrane is used as an actuating element for the pumps, valves and microfluidic chambers of the microfluidic network of the microfluidic card. It is inserted between the two layers 1, 2 of the card.

[0023] In reference to the Figure 1C, the microfluidic device D3 can also take the form of a microfluidic card 10 on one face of which is mounted a component 20 or microfluidic chip intended to be connected to the microfluidic network of the card. The microfluidic component advantageously has a section along X, Y which is smaller than the section of the microfluidic card along X, Y.

[0024] The term "microfluidic card" should be understood in a non-limiting manner and may cover all types of microfluidic device integrating a microfluidic network.

[0025] For example, the microfluidic component 20 may thus comprise a microfluidic network 201 connecting to the microfluidic network 101 of the microfluidic card. The microfluidic component 20 to be assembled on the microfluidic card 10 may be made of the same material as the microfluidic card 10.

[0026] A microfluidic card is used in the medical field to analyze a fluid, such as a liquid sample (blood for example) by connecting to an analysis machine. The microfluidic card can thus integrate an entire microfluidic network composed of microfluidic elements such as valves, chambers and microfluidic channels.

[0027] A microfluidic card can be made in a single layer or by assembling several layers together. Each layer can be machined so as to create at least a part of the microfluidic network of the card, the assembly of the layers by stacking making it possible to form the entire microfluidic network of the microfluidic card.

[0028] The microfluidic card has two main opposite faces, each extending in the two dimensions X, Y and has a low thickness (a few mm) along Z with respect to the other two dimensions.

[0029] The microfluidic card, in particular its two (or more) layers 1, 2, is advantageously made of a transparent material of the COP (Cyclo-Olefin Polymer), COC (Cyclo-Olefin Copolymer), PMMA (Polymethyl Acrylic Methacrylate), PDMS (Polydimethyl Siloxane), Silicon type...

[0030] The principle of the invention consists of assembling the two parts of a microfluidic device by inserting parylene between the two parts to be assembled. The assembly is carried out by applying at least one face of the first part of the device against one face of the second part of the device.

[0031] As a reminder, parylene or polyparaxylylene is a family of organic polymers which (in its basic form of Parylene N) is made up solely of hydrogen and carbon atoms. Parylene has the particularity of being hydrophobic and resistant to almost all chemicals. Parylene is more particularly in the form of a biocompatible polymer film which can be deposited on a surface, under vacuum after evaporation and transformation of its precursor.

[0032] In the context of the invention, parylene is referred to generically, but this of course covers all its derivatives.

[0033] It should be noted that parylene is a material that has transparency properties, suitable for allowing optical signals to pass through, used for example during analyses implemented in the microfluidic card.

[0034] In the case of a microfluidic device D1 such as a microfluidic card with at least two layers 1, 2, the parylene is added on the two opposite faces of the two layers to be assembled. This is the upper face of the lower layer 1 and the lower face of the upper layer 2.

[0035] In the case of a microfluidic device D2 integrating a deformable membrane 5 between two of its layers 1, 2 to perform the actuation functions, the membrane comprises a first layer of parylene on its upper face and a second layer of parylene on its lower face. In addition, the lower face of the upper layer 2 of the microfluidic card is coated with a layer of parylene, as is the upper face of the lower layer 1 of the microfluidic card. The membrane 5 is thus sandwiched between the two layers 1, 2 of the card.

[0036] In the case of a microfluidic device D3 produced on the basis of a microfluidic card 10 on which a microfluidic component 20 is added, a layer of parylene is added (over the entire surface or over at least part of the surface) on the upper face of the microfluidic card 10 and a layer of parylene on the lower face of the microfluidic component 20.

[0037] It should be noted that the parylene layer added to each part to be assembled is advantageously deposited over the entire face to be assembled. In the case of the microfluidic device D3, only the area for receiving the microfluidic component located on the upper face of the microfluidic card 10 can receive the parylene layer. But it could be deposited over the entire upper face of the microfluidic card 10.

[0038] The assembly of the two parts concerned is then implemented by thermal sealing, according to the manufacturing process described below. Manufacturing process

[0039] In a non-limiting manner, the method is described below for the assembly of a microfluidic component 20 on the upper face of a microfluidic card 10. The microfluidic card forms the first part of the microfluidic device and the microfluidic component forms the second part of the microfluidic device.

[0040] E1: A first layer 30 of parylene is deposited on one face of the microfluidic card 10, for example its upper face 100.

[0041] E2: A second layer 40 of parylene is deposited on one face of the microfluidic component 20, for example its lower face 200.

[0042] The deposition of each layer of parylene can be carried out in a thin layer, by a chemical vapor phase process (CVD).

[0043] It should be noted that the parylene layer can be deposited on each part of the device, without necessarily using a mask. During deposition, the parylene does not obstruct the microfluidic network of the card or that of the microfluidic component.

[0044] E3: The microfluidic component 20 is assembled on the microfluidic card 10 by applying the lower face 200 of the component (provided with its parylene layer) against the upper face 100 (provided with its parylene layer) of the microfluidic card.

[0045] E4: A thermal seal (T°) is carried out by mechanically holding the microfluidic component 20 against the microfluidic card 10. For example, the clamping with the thermal press is carried out by applying a force ranging from 500N to 1500N, preferably 1000N.

[0046] During the mechanical holding, the assembly is heated to melt the parylene, allow the two layers of parylene to adhere to each other and obtain the assembly of the microfluidic component 20 on the microfluidic card 10. The thermal sealing is for example carried out at a temperature between 110°C and 125°C, preferably around 118°C. In particular, care must be taken to remain below the glass transition temperature of the materials making up the microfluidic card 10 and the microfluidic component 20. For a material such as COC, this glass transition temperature is 135°C. During the thermal sealing, the heating is maintained for a period of between 5 minutes and 25 minutes, preferably a period of 15 minutes.

[0047] E5: A microfluidic device such as that shown in step E5 is thus obtained, with a microfluidic component 20 sealed on the upper face of the microfluidic card 10.

[0048] This produces a microfluidic device with two parts assembled together by adhesion of the parylene layers.

[0049] It should be noted that in the case of a microfluidic device D2 incorporating a deformable membrane 5 interposed between two layers 1, 2 of the card, the parylene layers are added over the entire membrane, even in the areas of the membrane that face a cavity of the card. Parylene also makes it possible to improve the sealing of the membrane in these areas, the membrane 5 being able to be porous to air.

[0050] The solution of the invention thus presents numerous advantages, among which: It is easy to implement; It limits the use of glues for assembly; It guarantees perfect sealing between the parts to be assembled;

Claims

1. Method for manufacturing a microfluidic device (D1, D2, D3), said microfluidic device comprising a first part and a second part to be applied against each other, the first part and the second part each comprising a so-called upper face and a so-called lower face, characterized in that it consists of: - Depositing a first layer (30) of parylene on the upper face of the first part, - Depositing a second layer (40) of parylene on the lower face of the second part, - Applying the first part against the second part so that the first layer of parylene is in contact with the second layer of parylene, - Carrying out a thermal sealing of the two parts against each other.

2. Method according to claim 1, characterized in that thermal sealing is carried out at a temperature between 110°C and 125°C.

3. Method according to claim 1 or 2, characterized in thatHeat sealing is achieved by holding the first part against the second part by applying a force between 500N and 1500N.

4. Method according to one of claims 1 to 3, characterized in that The heat seal is implemented for a period of between 5 minutes and 15 minutes.

5. Microfluidic device (D1, D2, D3) comprising at least a first part and a second part, assembled with each other, characterized in that this assembly is obtained by the method as defined in one of claims 1 to 4.

6. Microfluidic device according to claim 5, characterized in that the first part is formed of a first layer (1) of a microfluidic card and in that the second part is formed of a second layer (2) of the microfluidic card to be deposited on the first layer (1).

7. Microfluidic device according to claim 5, characterized in thatthe first part is formed of at least a first layer (1) of a microfluidic card and in that the second part is formed from a deformable membrane (5) which is applied by a first face against a face opposite said first layer.

8. Device according to claim 7, characterized in that the microfluidic card has a second layer (2) and in that the membrane (5) is interposed between the first layer (1) and the second layer (2) of the microfluidic card, and in that the membrane comprises a second face comprising another layer of parylene adhering to a layer of parylene deposited on a face opposite the second layer (2).

9. Microfluidic device according to claim 5, characterized in that the first part is formed by a microfluidic card (10) and in that the second part is formed by a microfluidic component (20) assembled on the card.

10. Microfluidic device according to claim 9, characterized in that the microfluidic card (10) comprises a first microfluidic network (101) and in that the microfluidic component (20) comprises a second microfluidic network (201), and in that the microfluidic component (20) is assembled on the microfluidic card (10) by establishing a sealed fluidic connection between the first microfluidic network (101) and the second microfluidic network (201).

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