HK1111658A - 3d structures based on 2d substrates - Google Patents

Description

Three-dimensional structure based on two-dimensional substrate

Technical Field

The present invention relates to a microfluidic device comprising a laminated structure or construction (hereinafter, these two terms will be used synonymously), and to a method for manufacturing such a microfluidic device.

Background

In addition to generally planar or two-dimensional microfluidic devices, multilayer microfluidic devices are also known which comprise at least one layer having a fluidic passage or channel or fluidic structure. These multi-layer devices or individual layers are fabricated by well-known techniques such as etching, injection molding, stamping, cutting, and the like.

For example, WO 01/25137 proposes the fabrication of modular three-dimensional microfluidic devices using multiple layers, most of which are fabricated and processed by an etching process (known for example from photolithography). In the proposed device, the fluidic channels are arranged in a plurality of layers, the channels being interconnected between the layers, thereby forming a three-dimensional fluidic network.

WO 99/19717 or U S6827906 respectively propose the fabrication of three-dimensional microfluidic devices comprising an array of microstructures. Transport of fluids through microchannels is achieved by electroosmotic flow or by electrophoresis. The microfluidic device is a multi-layer array, each layer being formed from a laminate that is drawn continuously from a roll and processed to create openings, reservoirs, flow channels, etc.

Furthermore, EP1542010 describes an analysis chip unit comprising a plurality of layers through which flow channels extend. A fluid sample is caused to flow through the flow channel (which is closed in cross-section) so as to be analyzed in accordance with the interaction between a predetermined substance and a specific substance disposed to face the flow channel. The chip also has a protruding member mounted on the flow channel. Thus, with the arrangement of EP1542010 a very accurate and efficient analysis of a fluid sample is possible.

A disadvantage of these known three-dimensional microstructures and the methods for producing them is that they can only be obtained by using various two-dimensional substrate layers or by complicated processes, such as several etching processes. In other words, these known three-dimensional microstructures are expensive to manufacture.

Disclosure of Invention

It is therefore an object of the present invention to provide a three-dimensional microfluidic structure that is constructed of a simple construction or structure. Another object of the present invention is a method of manufacturing a three-dimensional microstructure for a microfluidic device, by which a three-dimensional structure can be obtained at low cost.

In a first aspect, the invention relates to a method for manufacturing a microfluidic device as claimed in claim 1.

The method of the invention for manufacturing a microfluidic device comprising a laminated structure or construction made of a stack of layers is characterized in that: in order to form at least one layer comprising three-dimensional structures in a preferably planar two-dimensional layer, a specific two-dimensional pattern or two-dimensional structure is made by etching, stamping, cutting, laser cutting, roll cutting or by any other suitable method, followed by a mechanical and/or thermo forming step in order to form a three-dimensional structure corresponding to the two-dimensional pattern or two-dimensional structure.

Preferably the basic two-dimensional layer is constituted by an anisotropic substrate material on which the pattern for creating the three-dimensional structure is formed by a suitable method, such as stamping, cutting or etching, etc., and subsequently the substrate is shaped by applying a force such that the structural basic pattern is forced out of the two-dimensional substrate in order to form the three-dimensional structure.

The formation of the three-dimensional structure can be obtained mechanically or thermally or by other suitable methods.

The anisotropy (meaning that the properties depend on the direction) of the two-dimensional substrate must be such that, after shaping, the basic pattern initially formed on the substrate is forced out of the plane in that direction, so that the three-dimensional structure influences the microfluidic channels in the at least one layer which is arranged close to the further layer.

In a second aspect, the invention relates to a microfluidic device as claimed in claim 5.

The microfluidic device of the present invention comprises a multilayer laminated structure or construction comprising a plurality of layers, at least one of which comprises a microfluidic channel structure or microfluidic channel and at least one side of said layer is provided with a further layer comprising a so-called three-dimensional structure which influences the flow characteristics within the microfluidic channel or structure in the at least one layer.

The layer comprising the three-dimensional structure is obtained from a basic two-dimensional layer comprising an anisotropic material.

According to one possible design, the microfluidic device of the invention comprises at least four layers, such as a bottom layer, the further layer comprising the three-dimensional structure, the at least one layer comprising the microfluidic channel structure or configuration, and a top layer, the bottom layer and/or the top layer comprising at least one inlet opening and one outlet opening.

Further preferred designs of the microfluidic device according to the invention are defined in the dependent claims.

According to one possible example of the invention, the substrate material used may have different elastic modulus, bending strength or thermal stretch coefficient on both sides or surfaces thereof. But it is also possible that the substrate material used has physical properties on both sides that are different in other respects, such as different thermal conductivity, which can lead to different thermoforming by applying heat.

It is also possible to use materials with different conductive properties on both sides, so that by applying an electric current different heating is obtained on both sides of the substrate, which can also lead to different thermoforming.

According to a further alternative of the invention, for the at least one further layer comprising the microstructure, a layer of substrate material having an at least slightly increased thickness can be used. In this further layer with a slightly increased thickness, a three-dimensional pattern, including holes, channels, etc., can be produced by stamping, cutting, etching, laser cutting, etc. The three-dimensional features of the further layer are obtained by the at least slightly increased thickness of the further layer and the corresponding pattern-like structures.

Further embodiments of the inventive method are exemplified by the dependent claims.

Drawings

The invention will be described in more detail below by way of examples, which are illustrated in the accompanying drawings. In the drawings:

FIG. 1 schematically illustrates four layers to be combined by lamination for making an exemplary microfluidic device of the present invention;

FIG. 2 schematically illustrates a stack of layers of FIG. 1 for use in fabricating the microfluidic device;

FIG. 3 schematically illustrates the fabrication of a three-dimensional microstructure by deformation;

figure 4 shows a further possible way for manufacturing a three-dimensional microstructure layer by deformation;

figure 5 again shows a further possible way for manufacturing the three-dimensional microstructure layer by deformation;

figure 6 again shows a further possible way of manufacturing the three-dimensional microstructure layer by deformation;

figure 7 again shows a further possible way of manufacturing the three-dimensional microstructure layer by deformation;

FIG. 8 shows an example of a three-dimensional microstructure layer;

FIG. 9 illustrates the assembly of a microfluidic device of the present invention including the three-dimensional microstructure of FIG. 8;

FIG. 10 shows yet another design of a three-dimensional microstructure layer;

FIG. 11 again shows yet another possible design of a three-dimensional microstructure layer;

FIG. 12 shows yet another example of a three-dimensional microstructure layer;

FIG. 13a shows a further layer intended as a three-dimensional microstructured layer comprising a substrate of predetermined structure, having for example spots for detecting chemical properties;

FIG. 13b shows the expanded portion of the three-dimensional microstructured layer of FIG. 13a after formation;

fig. 14 shows a further possible way of producing a three-dimensional microstructure by cutting a substrate layer with an enlarged thickness;

fig. 15 shows a further three-dimensional microstructure based on a substrate layer with an enlarged thickness; and

fig. 16 shows yet another example of a three-dimensional microstructure having a substrate layer with an enlarged thickness.

Detailed Description

Fig. 1 schematically shows a possible example of a microfluidic device structure consisting of e.g. four different layers, such as layer 1, which layer 1 comprises a microfluidic channel structure 3, along which microfluidic channel structure 3 e.g. sample fluid flows through various sections, compartments, reservoirs, etc. for processing in a predetermined manner. A further layer 11 is shown immediately after the layer 1 with the microfluidic channels, which layer 11 comprises a three-dimensional microstructure 13. Each of these out-of-plane extensions of the microstructure 13 affects the flow characteristics of the fluid sample through the microchannels 3 in the layer 1, in order to ensure, for example, proper mixing of the fluid sample as it flows through the channels 3, dissolution of solid components within the fluid, influence flow resistance, etc.

Finally, a top layer 31 and a bottom layer 21 are arranged on both sides of the two layers 1 and 11 in order to complete the microfluidic device on both sides. An inlet opening 33 and an outlet opening 35 are provided in the top layer 31 for injecting samples and for collecting the test samples that are eventually processed, reacted and/or analyzed.

In fig. 2 it is schematically shown how these four layers 1, 11, 21 and 31 can be combined, for example by laminating the layers.

According to the method of the invention, the three-dimensional structure may first be fabricated from a suitable two-dimensional substrate (e.g. a thin film or a metal plate) independently of the device comprising the microfluidic channel, and then combined with other layers to form said microfluidic device. Of course, the three-dimensional structure is preferably fabricated according to the design of the microfluidic channel. Possible methods for forming and forming the substrate for fabricating the three-dimensional structure will be described in detail below with reference to other figures. Common to all methods is that the planar two-dimensional substrate is first structured by using a suitable method in order to produce the basic form of the microstructure. Then, according to one possible method, the substrate is shaped such that the structured basic pattern is forced out of the two-dimensional substrate in order to obtain the three-dimensional structure. For structuring the substrate, various known methods are suitable, such as etching, laser cutting, conventional cutting, stamping, micro-structured cutting by using a cutting roll, and the like. The deformation of the two-dimensional structure may be performed mechanically or thermally, or by using other suitable methods. Basically, it is preferred to use a planar substrate which may have anisotropic direction-dependent properties, i.e. properties which form a directional force, which is preferably perpendicular to the plane of the substrate, in order to facilitate an out-of-plane deformation of the structural pattern in the planar substrate. Preferably, the anisotropy in the substrate is such that the pre-structured pattern is finally pressed towards the same side of the two-dimensional substrate by applying a corresponding force.

One possible deformation technique is mechanical forming, which will be described with reference to figures 3 to 7 later. Fig. 3a shows a planar two-dimensional substrate 11, in which the respective structure pattern 12 is produced by a suitable method, for example cutting. By applying a deforming force, the pattern 12 of the predetermined configuration is forced out of the plane 11' so as to create a protruding portion 13 as shown in fig. 3 b. The deformation can be achieved, for example, by a simple bending movement of the plane 11, by pressing the substrate 11 against a roller or an edge, or by applying a deforming force, etc.

Similarly, a three-dimensional structure 11' as shown in fig. 4b and 5b can be obtained by mechanical deformation starting from the respective planar two-dimensional substrate 11 shown in fig. 4a and 5 a.

Mechanical deformation is also used to obtain a three-dimensional structure as shown in fig. 6b and 7b, wherein instead of applying a bending or deforming force, an elongation force can be applied according to the two arrows K shown in fig. 6 b. The basis of the three-dimensional structure is also a planar two-dimensional substrate 11, in which substrate 11 respective structures 12 are produced, as shown in fig. 6a and 7 a. Of course, instead of a tensile force, a bending force can be applied again, which can be used in particular for producing the three-dimensional structure of fig. 7 b.

In fig. 8, a perspective view of an example of a three-dimensional structure is shown, in which each microstructure 13 is formed on a substrate 11'.

Fig. 9 shows the assembly of an embodiment of a microfluidic device corresponding to the device shown in fig. 1 and 2. The basis for the microfluidic device is also a planar two-dimensional plate similar to layer 1 in which the microfluidic channel structure 3 is arranged. Microfluidic channel structures include various channels, reservoirs, mixing regions, and the like. In order to influence the flow of the sample flowing along the channel passage 3 in the further layer 15, a three-dimensional microstructure 13 is also arranged, which three-dimensional microstructure 13 can be introduced into this layer 15 by inserting a substrate 11 ', which substrate 11' comprises the three-dimensional microstructure 13 as shown in fig. 8. Finally, the microfluidic device of fig. 9 comprises a bottom layer 21 and a top layer 31, which top layer 31 comprises an inlet opening 35 and an outlet opening 33. Of course, instead of only one three-dimensional structural layer 11', another three-dimensional structural layer may also be arranged on this layer 15 in order to influence the flow of the fluid sample along the channel or flow path 3.

Instead of mechanically or thermally shaping a planar two-dimensional substrate 11 to obtain a three-dimensional microstructure, a three-dimensional structure may be made by processing one side of the planar substrate 11 with a special tool (e.g. a shaping tool) to obtain shaped structures 17 and 18 as schematically shown in fig. 10 and 11. The chute 17 is shown in fig. 10, while the broken transverse slot 18 is shown in fig. 11. The distance between the grooves may be, for example, 10-100 μm and the depth of the grooves may be, for example, 30 μm. Typically, the angle of the slot in fig. 11 may be, for example, 45 °.

It is also possible to have a so-called pillar array 19 instead of the grooves, as schematically shown in fig. 12. These pillar arrays may be manufactured, for example, by etching in accordance with a photolithographic process. The distance between the pillars 19 may be, for example, 200 μm, the diameter of the pillars may be, for example, 100 μm, and the height of the pillars may be, for example, 50 μm.

The structures shown with reference to fig. 1 to 12 are typically used in microfluidic devices. Preferably, these three-dimensional microstructures are used in devices having a layered structure, by which is meant a device having multiple layers. As described with reference to fig. 1, 2 and 9, these devices include a base as a bottom layer, a top layer, one or more layers having microfluidic pathways, and one or more layers having the three-dimensional structures described in the present invention.

Preferably, the device of the invention is used as:

mixing structures, for example so-called fish-ridges, for homogeneously mixing a sample liquid with one or more solvents and/or reagents, or for mixing two or more components, or for forcing the sample liquid to have a specific flow rate, or for changing the flow resistance in the channel.

A dissolution profile, which is a profile enabling mass transport in a direction perpendicular to the direction of flow of the sample liquid, thus enabling, for example, drying shrinkage components sticking to the channel bottom of the microfluidic channel to be distributed evenly over the entire channel square cross-section. Furthermore, by using this three-dimensional microstructure, it is generally possible to better enable the solid components in the fluidic channel to be dissolved by the liquid sample, or the dried-out components in the channel to be wetted and dissolved again by using a solvent.

Another effect of using the three-dimensional microstructure is to influence the flow, velocity or resistance, respectively, of the fluid moving in the channel and to achieve a specific flow profile in the microfluidic channel.

For example, the dried-out components in the middle of the channel can be dissolved without risk by using microstructures, which, under the influence of capillary action, will accumulate on the channel walls. Once accumulated, the constituents will be difficult to extract from the wall because of the reduced flow velocity there (due to the parabolic flow profile).

A dissolution structure (e.g., the array of posts shown in fig. 12) can facilitate dissolution of the desiccating components within the channels because the desiccating components do not dry out in a compact volume. Since the dissolution zone with the dry-shrink component provides multiple base points for the solvent as the microstructure of the pillar array, the dry-shrink component can dissolve faster than without the structure.

A further use is micro-optical use obtained by producing so-called micro-mirror arrays in order to obtain confocal optical detection in a micro-fluidic channel. In this respect, we refer to fig. 13a and 13b, which schematically show another dedicated three-dimensional microstructure. In fig. 13a, a triangular structure pattern 12 is shown on a planar substrate 11, the structure pattern 12 comprising detection points 14 at the peaks of the respective triangles. By applying a bending or twisting force, the triangles will be forced out of the plane 11 so as to create an upwardly curved triangular shaped part 13, which part 13 comprises a detection point 14 at the peak of each peak. By applying a specific illumination step (e.g. a light beam directed at the bending part 13 along a specific angle) light can be reflected from the detection spot 14, so that the background signal of parts that are not bent will be reduced. Another method for reducing the background signal of the unbent part is to focus the detection light on the curved part only in a confocal manner, which means that all light outside the focal point is shielded.

By positioning the spot (e.g., only a portion of the spot) to cover the bend, the effective spot size (the portion of the spot that is in the bend position) is reduced compared to the total spot area. This enables a smaller effective spot to be produced without the need to reduce the overall size of the spot area.

The fluid sample to be analyzed in the present invention may be, for example, a prepared human or animal body fluid, such as blood.

It is also possible to create a three-dimensional microstructure by using a further layer, the layer thickness of which is preferably sufficiently larger than the thickness of the layer comprising the microfluidic channel, for example. Examples of layers with increased thickness are shown in fig. 14 to 16. The structure pattern 42 is formed in the substrate 41 with increased thickness, for example by using a dicing blade, as shown in fig. 14 a. By punching out the formed structure 42, holes 49 in the substrate layer 41 will be formed, as schematically shown in fig. 14 b. In a similar manner, microstructured three-dimensional patterns 44 and 46 can be formed, as schematically illustrated in fig. 15 and 16. Furthermore, the substrates as shown in fig. 14 to 16 may be combined with layers comprising microfluidic channels in order to produce microfluidic devices similar to those described in fig. 1, 2 and 9. Needless to say, the structures shown in fig. 14-16 can also affect the flow of a liquid sample within a channel or passage in a microfluidic layer that is disposed immediately adjacent to (e.g., on top of) the three-dimensional structure.

A great advantage of the present invention is that the three-dimensional microstructure of the microfluidic device does not have to be aligned in a very precise manner with respect to the layer containing the channels. The three-dimensional microstructure can be produced independently of the structure containing channels. The two structures are then placed together by overlapping the two layers. This reduces the need to align the two layers during assembly of the final microfluidic device.

Fig. 1 to 16 show and describe only examples of three-dimensional microstructures and microfluidic devices using the three-dimensional microstructures of the present invention, and other designs and other combinations may be used to fabricate microfluidic devices. Importantly, the three-dimensional microstructures are fabricated in separate layers and combined with other layers into microfluidic devices. In other words, it is not necessary to build multiple layers on one substrate, for example using multiple etching steps, as is known in the art of lithography. Furthermore, it is not necessary to use multiple layers to obtain the three-dimensional structure, but the three-dimensional structure may be achieved by using one layer and then by, for example, mechanical or thermal treatment (as described above). Instead of mechanical, thermal or chemical treatment, it is also possible to use a substrate layer with an increased thickness to obtain the three-dimensional structure.

By using the method of the invention and the three-dimensional structure of the invention, three-dimensional multifunctional microstructures can be obtained in a simple manner without the need to use masks to construct multiple layers (as known in the art). By using the three-dimensional microstructure, the manufacturing cost for manufacturing the microfluidic device can be lower. Furthermore, the three-dimensional microstructure may be varied according to the function of the microfluidic channel or structure, respectively, depending on the flow rate, flow velocity, microfluidic function, various fluid samples used, dry components used, chemical reaction, etc.

Claims (9)

1. A method for manufacturing a microfluidic device comprising a laminated structure made of laminated layers, wherein:

in order to form at least one layer comprising three-dimensional structures in a preferably planar two-dimensional layer, a specific pattern or two-dimensional structure is made by etching, stamping, cutting, laser cutting, roll cutting or by any other suitable method, followed by a mechanical and/or thermo forming step in order to form a three-dimensional structure corresponding to the two-dimensional pattern or two-dimensional structure,

the method is characterized in that:

the basic two-dimensional layer used to form the three-dimensional structure layer is composed of an anisotropic material, and the two-dimensional layer is processed by mechanical or thermal forming such that the two-dimensional pattern or two-dimensional structure is forced out of plane to form the three-dimensional structure.

2. The method of claim 1, wherein: the two-dimensional layer is bent, or pressed against an edge, or rotated by applying a twisting force, such that the pattern or structure originally formed in the two-dimensional layer is forced out of plane to form the three-dimensional structure.

3. The method according to claim 1 or 2, characterized in that: at least one layer comprising the three-dimensional structure is combined with or arranged next to a layer comprising the microfluidic channel structure such that the three-dimensional structure affects the flow of fluid through the microfluidic channel.

4. The method of claim 3, wherein: at least four layers are combined to make the microfluidic device, the four layers comprising a bottom layer, at least one layer comprising the microfluidic channel structure, at least one further layer comprising the three-dimensional structure and a top layer, and the bottom layer and/or top layer comprising at least one inlet opening and one outlet opening.

5. A microfluidic device comprising a laminated structure comprising a plurality of layers, at least one of the layers comprising a microfluidic structure or a microfluidic channel, wherein: at least one side of said layer is arranged with a further layer comprising a three-dimensional structure such that the three-dimensional structure influences the flow characteristics of a fluid in the microfluidic channel, the further layer being obtained from a two-dimensional substrate comprising an anisotropic layer material.

6. The microfluidic device of claim 5, wherein: the three-dimensional structure in the further layer may be obtained by mechanically or thermally shaping the two-dimensional substrate comprising the anisotropic layer material.

7. The microfluidic device of claim 5, wherein: the further layer comprising the three-dimensional structure comprises an at least slightly increased thickness.

8. The microfluidic device according to any one of claims 5 to 7, wherein: the device comprises at least four layers, such as a bottom layer, the further layer comprising the three-dimensional structure, the at least one layer comprising the microfluidic structure, and a top layer, the bottom layer and/or the top layer comprising at least one inlet opening and one outlet opening.

9. The microfluidic device of claim 5, 6 or 8, wherein: the three-dimensional structure in the further layer may be obtained by applying a bending or twisting force to a preferably planar two-dimensional structural layer having different physical and/or thermal properties on both sides thereof, such that by applying the bending or twisting force the structure is forced out of the two-dimensional plane in order to create the three-dimensional structure.