Description

The invention relates to a method for manufacturing a structure with at least one microchannel for fluid. The invention also relates to a microfluidic device.

A method for manufacturing a structure with at least one microchannel for fluid is known from US 6.595.232 B2. This known method uses a mixture which is thermoformed by using a mold onto a substrate to form a first assembly. The first assembly is assembled with a second assembly comprising a second substrate, wherein the first assembly and the second assembly form a structure with at least one microchannel (recess) between the first and the second substrates. The known method for manufacturing a structure with microchannels for fluid is relatively complex and/or time-consuming.

Hence, it is an object of this disclosure to provide a less complex, more efficient and/or less time consuming method for manufacturing a structure with at least one microchannel for fluid.

This object or at least a part thereof is achieved by the method as defined in claim 1.

The method for manufacturing a structure with at least one microchannel for fluid comprises the following steps:

- providing a substrate;

- providing at least one embedded open microchannel in a non-planar substrate surface of the substrate;

- sealing the at least one embedded open microchannel by a sheet by connecting the sheet to the non-planar substrate surface to obtain the structure with the at least one microchannel for fluid.

The substrate may be provided via 3D printing, injection molding, micro milling, hot embossing or any other applicable technique. By using these techniques for providing a substrate, the at least one embedded open microchannel in a non-planar substrate surface of the substrate may be provided simultaneously. Alternatively, the at least one embedded open microchannel in a non-planar substrate surface of the substrate may also be provided in a separate step after forming the substrate. In such a separate step for providing the microchannel a different technique may be used than the technique used for providing the substrate. The microchannel is provided directly in the substrate’s surface. In other words, a groove-like open microchannel is provided. An opening into the open microchannel is defined by edges between interior microchannel walls and the substrate’s surface. Such an open microchannel is provided in a relatively efficient and/or relatively minimal time consuming manner. The method according to this disclosure allows to seal these open channels with an inexpensive, fast and reliable method to be discussed in more detail below to provide the structure with a microchannel.

In addition, the substrate surface in which the open microchannel is provided has topography, i.e. the substrate surface is non-planar (not lying or able to be confined within a single plane). As a result, the opening of the groove-like open microchannel formed in this non-planar substrate surface is not planar, i.e. the opening of the microchannel defined by the edges does also not lie in one plane, but lies at least in two planes or even more planes. Such a microchannel configuration is not known from US 6.595.232 B2. The recesses (channels) known from US 6.595.232 B2 comprise a virtual longitudinal center line which is a straight line, i.e. each side of each recess is a planar surface. A planar surface is a surface in one plane in which if any two points are chosen a straight line joining them lies wholly in that surface. A non- planar surface is a rounded surface or a surface comprising at least two adjacent angled planar surfaces, wherein the angle between the two adjacent planar surfaces is smaller or larger than 180 degrees, i.e. not 180 degrees. For example, a cuboid substrate has a non-planar surface between one of the transitions between the sides of the cuboid substrate. Hence, the method according to this disclosure removes the restriction of planar configurations for microfluidic channels and provides an easy and cheap way to create new structures and/or new 3-dimensional microfluidic devices.

Further, the structure is manufactured by means of using a sheet which is used to seal in a relatively reliable manner the at least one embedded open microchannel by connecting the sheet to the non-planar substrate surface to obtain the structure with the at least one microchannel for fluid.

In one aspect, the sheet may be a thermoplastic sheet which is heated before sealing the at least one embedded open microchannel. By heating the thermoplastic sheet, for example to approximately its glass-transition temperature, the sheet becomes more soft such that the sheet can better take the shape of the non- planar substrate surface. In addition or alternatively, an improved and reliable connection between the sheet and the substrate surface may be obtained by heating the thermoplastic sheet. In addition, the heated thermoplastic sheet may be stretched before sealing the at least one embedded open microchannel which may also enhance the capability of adapt to the shape of the non-planar substrate surface and/or to reduce the risk of leakage. The substrate may at least partly be made from a thermoplastic, wherein at least the thermoplastic non-planar substrate surface of the substrate may be heated, for example to approximately its glass-transition temperature, before connecting the thermoplastic sheet to the thermoplastic non- planar substrate surface. This may further improve the (sealing) connection between the sheet and the thermoplastic non-planar substrate surface, and/or may further reduce the risk of leakage from the microchannel.

In a different aspect, the sheet is applied to the non-planar substrate surface by using vacuum. Using vacuum to seal an open micro channel on a topographic surface of the substrate by means of a sheet provides excellent results in a cost effective manner. The vacuum to be applied between the sheet and the substrate surface will pull the sheet against the substrate surface. The vacuum can be applied for example by vacuum forming or vacuum thermo-forming. While the sheet is able to accurately follow the macro-topography of the substrate by using vacuum, the sealed microchannel will remain free, as the sheet will not enter the relatively small space of the microchannel. It is also possible to use pressure forming, wherein vacuum and pressure on opposing sides of the sheet are used to provide the structure with the microchannel. After applying the thermoplastic on the non-planar substrate surface by means of the vacuum, the vacuum can be released and the thermoplastic has taken the topographic shape of the non-planar substrate surface while closing the microchannel, i.e. closing or covering at least the opening of the microchannel defined by the edges as discussed in this disclosure.

The risk of the sheet entering the microchannel may further or alternatively be reduced if the width of an embedded open microchannel is equal to or smaller than the thickness of the sheet used for sealing the microchannel. Preferably the thickness of the sheet is equal to or less than 2 mm, more preferably 1 mm. For example, a thickness of the sheet of 500 micrometre will provide excellent results, because such a sheet will follow the non-planar substrate surface perfectly, but is also “thick” enough that it will not intrude easily in a microchannel having the same width as the thickness of the sheet or a smaller width.

The non-planar substrate surface of the substrate surrounding the at least one embedded open microchannel may be provided with an adhesive before sealing the at least one embedded open microchannel with the sheet. In this way the connection between the sheet and the substrate may be improved and/or the risk of fluid leakage in use may be reduced.

In a further aspect, the thickness of the substrate may be at least two times thicker than the thickness of the sheet, preferably at least three times thicker, even more preferred at least four times thicker.

The invention also relates to a microfluidic device which includes at least one structure manufactured according to the method as disclosed in this disclosure. In particular, the microfluidic device can consist of a single structure or of a set of such structures assembled together. In the latter, each structure can be referred to as a module, wherein the channels of the modules may communicate with each other and/or with the outside of the device so that within the device there is to be found at least one (liquid or gaseous) fluid circulation circuit which may communicate with the outside via at least one inlet and one outlet. It is also possible that the microfluidic device does not have an outlet, in which case the fluid remains inside the device and capillary forces may be used to transport the fluid. Besides at least one channel, the structure to be used in a microfluidic device may comprise a distribution chamber, or (chemical, biological, electrochemical) reaction chamber, and/or functionalization by the use of additional parts such as electrical conductors, electrodes, light conductors, and the like. Such parts can be used as heater mechanisms, sensors, and the like.

The method and the structure will be explained in more detail below with reference to the appended figures showing an exemplary embodiment, in which:

Figures 1 A-C show cross section views of the steps for manufacturing a structure with at least one microchannel for fluid; Figures 2A,B show perspective views of the steps for manufacturing the structure with at least one microchannel for fluid as shown in figure 1C.

In the following description identical or corresponding parts have identical or corresponding reference numerals. Each feature disclosed with reference to a specific figure can also be combined with another feature disclosed in this disclosure, unless it is evident for a person skilled in the art that these features are incompatible.

The figures show in a schematic manner the manufacturing process of a structure 100 with one microchannel 102’ for fluid. Of course, it is possible to provide the structure 100 with more than one microchannel for fluid. The method comprises the following steps as shown in the figures:

- providing a substrate 101 as shown in figures 1A,2A;

- providing at least one embedded open microchannel 102 in a non-planar substrate surface/side 105 of the substrate 101 , wherein in the example as shown in figures 1A,2A the substrate has already been provided with the least one embedded open microchannel 102 in one side (upper side) 105 of the substrate 101 and a sheet 103. Fig. 1A shows the sheet 103, but it is noted, that the step of providing a sheet 103 follows the step of providing at least one embedded open microchannel 102. Figures 2A,B demonstrate that the microchannel 102, 102’ is embedded/arranged in the substrate 101 and provided in the substrate surface/side 105. In fig. 2A it is shown that the microchannel 102 is open, i.e. an upper side of the microchannel 102 is open. An opening into the open microchannel is defined by opposing edges 104 between interior microchannel walls and the substrate surface/side 105. The edges 104 extend in the longitudinal direction of the elongate microchannel 102. The opening defined by the edges of the microchannel 102 is provided in the non-planar substrate side 105 and the opening lies at least in two (virtual) planes. For example, a first plane extending parallel to bottom side surface 106 of the substrate 101 and a second plane provided by a side of cuboid 120 such that the first and the second plane of the opening are aligned substantially perpendicular to each other. A curved (or rounded) surface provided by a half of a cylinder 130 is also possible as shown;

- sealing the at least one embedded open microchannel 102 by a sheet 103 by connecting the sheet 103 to the non-planar substrate surface/side 105, as shown in figure 1 B, to obtain the structure 100 with the at least one microchannel 102’ for fluid as shown in figures 1 C, 2B. As shown the sheet closes or covers the upper side of the microchannel 102, i.e. closes or covers the opening defined by the edges 104.

The new approach consists in more detail of providing a substrate

101 , which can be 3D-printed, injection moulded, hot embossed or micro-milled or manufactured with any other applicable technique. The substrate 101 comprises in the example shown in the figures an open groove-like microfluidic channel 102 (see figures 2A,B) on its top substrate surface 105. The open channel 102 is in the embodiment shown sealed by using a vacuum forming process or a pressure forming process (not shown) that stretches a heated thermoplastic sheet (or foil) 103 over the multi-planar top substrate surface 105. Arrows 110 indicate vacuum used to bring and/or connect the sheet 103 to the non-planar substrate surface 105. Curved lines 115 indicate heating the sheet 103, in particular the thermoplastic sheet. Arrows 116 indicate the forces working on the sheet as a result of the vacuum between the sheet 103 and the non-planar substrate surface 105. The thickness of the thermoplastic sheet 103 ensures that the process accurately follows the macro-topography over the multi-planar top substrate surface 105 instead of entering into the microchannel. The risk of the sheet 103 entering the microchannel 102 is for example reduced if the width measured in the direction indicated in figure 2A by arrow W of an embedded open microchannel 102 is equal to or smaller than the thickness (measured in the direction indicated in figure 1A by arrow T) of the sheet 103 used for sealing the microchannel

102. The width of the microchannel 102, 102’ is defined by the distance between two opposing edges 104, i.e. the distance traverse to the longitudinal direction of the elongate microchannel 102, 102’. The thickness T of the sheet 103 is the smallest dimension of the sheet 103. Preferably, the thickness of the sheet is equal to or less than 2 mm, more preferably between 0,2 - 1 mm. In figure 2A, 2B the width of the microchannel is overly large shown, i.e. the dimensions of the microchannel with respect to the sheet and substrate as shown in the figures are smaller. Typically the width W of the microchannel ranges between 100-1500 micrometre, preferably between 100-1000 micrometre. The depth of the microchannel has corresponding dimensions. The thickness T of the sheet 103 in the example shown in the figures is for example 500 micrometre. The thickness of the substrate 101 is at least 2 mm, preferably at least 3 mm. The thickness of the substrate 101 is the smallest dimension of the substrate 101. The substrate 101 or at least a part thereof including surface 105, may be made of thermoplastic such that at least the thermoplastic non-planar substrate surface 105 of the substrate may be heated, for example to approximately its glass-transition temperature, before connecting the thermoplastic sheet 103 to the thermoplastic non-planar substrate surface 105.

After or before the step shown in figure 1A, the non-planar substrate surface 105 of the substrate 101 surrounding the at least one embedded open microchannel 102 may be provided with an adhesive before sealing the at least one embedded open microchannel 102 with the sheet 103.

Instead of using vacuum, the sheet 103 may also be moved and applied to the non-planar substrate surface 105 of the substrate by using pressure only on the side of the sheet facing away from the substrate 105. The pressure may work on the sheet 103 in a manner similar as represented by the arrows 116 shown in the figures.

Instead of using a partly thermoplastic substrate, the substrate may also be made from other materials. For example, the substrate may be made from metal. Also materials normally used in 3D printing besides thermoplastic can be used for manufacturing the substrate, such as methacrylate photopolymers.

The substrate has a fluid inlet 112 and a fluid outlet 114, such that fluid can be introduced in the at least one microchannel 102 via the fluid inlet 112 and discharged from the microchannel 102’ via the fluid outlet 114. Hence, the method of this disclosure also comprises steps of providing a fluid inlet 112 and a fluid outlet 114 in the structure 100. In such a structure 100 fluid can be introduced, wherein the fluid may flow through the least one microchannel 102.

In the embodiment shown in the figures the non-planar substrate surface 105 is provided by an outer top side of the substrate 101 with multi-planar topography, i.e. multi-planar topography provided by a cuboid 120 and the half of a cylinder 130. However, it is also possible to provide other sides, for example the bottom side surface 106 with a multi-planar topography. Further, the invention can also be applied on substrate shapes having flat sides only, such as a cube (not shown). The non-planar substrate surface is then provided by at least two adjacent outer sides of the substrate, for example for a cuboid substrate the top side and a side of the substrate between the top side and the bottom side. The microchannel is then provided at least partly in the top side and at least partly in the side, such that the microchannel is located in two planes. For the cuboid 120 and/or in the two adjacent outer sides of the cuboid substrate at least one fillet or chamfer may be used to reduce the risk of leakage. A fillet, chamfer or similar solution may be used to replace a 90 degrees edge/corner with corners with a slightly smoother transition, i.e. less or more than 90 degrees.

Further, the invention relates to a microfluidic device (not shown) comprising at least one structure 100 manufactured by the method as disclosed herein. Topographical microfluidic channels expand the form factors for designing a microfluidic device. This means next to a planar application, the microchannels can now be applied in any form of topography. Expanded form factors due to the method as disclosed herein can be utilized to easily adapt microfluidic devices to fit in- or onto established devices in a way that they can be used together in novel ways. For example a microfluidic chip can be easily take the shape of a cuvette which enables it to be used in every standard uv-vis spectrophotometer. This new possibility to adapt microfluidic devices to established technical devices is due to the greater potential form factors. Furthermore, it is interesting for Point-of-Care diagnostic microfluidic devices, as the microchannel could be integrated into the device casing and may reduce the cost of the device. It also enables a relatively simple and reliable fabrication of connections from one microfluidic part to the other, as this can be seamlessly achieved in one design. Being able to create microfluidic channels that follow geometry of the substrate may also contribute to provide more compact microfluidic devices as the microchannel(s) can for example go around a cube and use all of its sides. Using more than one or all sides of a substrate instead of just a single side may also increase the interfacing surface advantageously, for example for heat exchange by using the micro-channels around a copper block.