HK1110260A - Microfluid system and method for production thereof - Google Patents

Description

Microfluidic system and method of manufacturing the same

The invention relates to a microfluidic system having a carrier body, preferably provided with a piercing device, and a semi-open microchannel arranged on the carrier body for the capillary transport of a fluid from a removal point to a target point. The invention also relates to a preferred use of such a system and to a method for producing the system.

Systems of this type can be used exclusively in bioanalysis for testing of the smallest quantities of fluid which are removed in situ as capillary blood, for example in order to determine the blood glucose. In this case, the microfluidic technology is characterized by smaller and smaller dimensions of the structural components, in addition to microscopic volumes (microliters and less), which can utilize capillary forces and must be cost-effective in terms of what is known as disposable (disposable) and must be suitable for mass production. Although the field of semiconductor technology has disclosed methods for highly integrated systems exclusively in the form of mask etching ("photochemical etching"), the materials used in this field are scarcely suitable for mechanically stressed structures, mainly because of their brittleness. When etching biocompatible materials such as steel, the problem arises that the resulting cross section of the channel structure does not convey the fluid particularly optimally, due to the homogeneous material removal. The method of using humectants which has been proposed in this connection in US-A2002/0168290 is also problematic for the following reasons:

the need for an additional production step,

compatibility with the method of verification of the analyte in the sample being delivered (i.e. no effect or unacceptable distortion on the measurement).

Often even biocompatibility (without any toxic effect) is necessary, since the short passage of the parts into the organism when coated with wetting agents cannot be ruled out at the time of sampling.

The hydrophilization must be sufficiently storage-stable.

There are physical limitations in the exclusive use of humectants without suitable geometry. Such restrictions exist singly or in combination within the required transport distance, positional/gravitational irrelevancy and/or flow velocity.

Starting from this, the object of the invention is to avoid the disadvantages occurring in the prior art and to improve the system and the production method in such a way that a structure for the effective transport of small amounts of fluid is provided by advantageous measures. In particular, the possible limitations due to the use of wetting agents exclusively should be reduced.

To achieve this object, the invention proposes a combination of features which is specified in the independent claims. Advantageous embodiments and refinements of the invention result from the dependent claims.

Accordingly, in the case of microfluidic systems, it is proposed to coat the stent body with a structural layer for fluid transport, which defines microchannels at least in the upper region and laterally, except in the bottom region. The coating can be applied in a simple manner with a previously intangible substance to form a permanently adhering structure, wherein the fluid-conducting function, which is based on the increased capillary action, is achieved by forming channels or elevated channels in the structural layer or on its side walls. This means in particular that channel cross sections with high dimensional ratios can also be achieved on homogeneous etchable substrates, which greatly improve the capillary action. In this case, the holder body can simultaneously be designed as a piercing element for piercing the skin or can perform a sampling or receiving function separate from the piercing element.

In an advantageous embodiment, the microchannel has a lower cross-sectional area provided in the carrier body, preferably already engraved, and an upper cross-sectional area formed in the structural layer thereon. It is also possible for the structural layer to laterally delimit the microchannel over its entire depth and thus to assume only the function of conducting fluid.

It is particularly advantageous if the structural layer consists of a photoresist, preferably a thick-film photoresist. In this way, a micro-flow-guiding structure with the required stability and inertia for the intended use can be realized on the support body in a simple manner. This can be achieved by the optoelectronic structuring (optostrikturriert) of the structured layer in order to form or increase the microchannels, so that a complex geometry with the required precision can also be provided.

The structural layer advantageously has a layer thickness of more than 50 μm, preferably 200 to 500 μm.

Another inventive aspect of the present invention is that the microchannels have a plurality of partial cross-sections that are etched deep from the surface of the stent body by successive etching steps. It is also possible to achieve high aspect ratios of the microchannels in a homogeneous etchable support body material in this way. It is particularly advantageous if this size ratio is greater than 0.5, preferably greater than 0.8.

It is advantageous for the fluid transport of the individual capillaries if the microchannels have a clear width in the range of 50 to 500 μm.

A further advantageous embodiment provides that a partial cross section in the support body is formed by etching through a photochemical mask.

According to a further variant of the invention, the capillary action can be increased by the microchannel having undercuts which are preferably formed in the region of its longitudinal edges by means of bottom-side etching.

In a further embodiment, the carrier body is made of a homogeneous etchable material, wherein the desired properties, such as advantageous workability, stability, inertia and biocompatibility, can be achieved, in particular, using a planar shaped part, preferably made of metal, in particular high-grade steel.

Advantageously, the stent body formed from a flat material has a thickness of 100 to 450 μm, preferably 150 to 300 μm.

It is also advantageous if the structural layer has additional substances or components which increase the hydrophilicity, or the wettability of the walls of the microchannels is increased by chemical surface treatment.

In a further development, at least one partial structure of the carrier body, preferably the piercing means, is formed outside the microchannel region by etching or punching, so that different structuring can be provided by a uniform process.

A preferred use case relates to a disposable sampling element comprising a microfluidic system according to the invention.

Another preferred application of the microfluidic system according to the invention consists in the transport of a sample fluid from a removal location to a destination location, in particular to a detection area.

In terms of method, the object stated at the outset is achieved by the fact that the fluid-carrying microchannels are raised or formed by a photoresist layer, in particular a thick-film photoresist, which is applied to the carrier body.

In an advantageous embodiment, the photoresist is sprayed or scratched (aufgerakelt) as a thick film onto the stent body or is applied to the stent body by means of a dip coating.

A further advantageous measure consists in that the first photoresist layer engraves the microchannels into the carrier body by means of mask etching; and a second photoresist layer is applied after the first photoresist layer is removed and is structured photoelectrically in order to increase the microchannels.

The invention will be explained in more detail below with the aid of embodiments that are illustrated in the drawing.

These figures are:

figure 1 is a perspective view of a sampling element as a microfluidic system for delivering a sample fluid,

figures 2 to 4 are cross-sectional views of a system according to figure 1 with microchannels having different structural layers,

FIGS. 5a to f are cross-sectional views of the system according to FIG. 1, wherein the successive method steps of the system for the optoelectronic structuring of the buildup channels are shown,

fig. 6a to k are successive method step diagrams corresponding to fig. 5 for the channel deepening.

The microfluidic system shown in the figures is capable of sampling as a disposable sampling element 10 and of capillary transport of small amounts of body fluids. To this end, the system comprises a planar stent body 12, a piercing mechanism 14 formed thereon, and a capillary-type microchannel 16, which is at least partially defined by a structural layer 18 of the stent body 12.

The support body 12 is made of steel having a thickness of approximately 150 to 300 μm as a strip-shaped planar shaped piece. Its adjacent end section forms a support area 20 for handling during the perforation process, while the integrally formed lancing mechanism 14 at the distal end creates a small wound in the skin of the user to enable the removal of minute amounts of blood or interstitial fluid.

The microchannel 16 is fluted or semi-open along its length so that it can be fabricated photolithographically as described below. The sampling site 22 in the area of the puncture device (puncture tip 14) effectively removes fluid from the skin or skin surface over a half-open cross section, while the tissue portion does not completely close off the entry cross section as in conventional hollow catheters.

The fluid is transported via the capillary channel 16 to a target site 24 spaced from the lancing mechanism 14, where the body fluid can be analyzed. Such an analysis can be carried out in the known manner, for example, by means of a spectroscopic or electrochemical verification method.

The channel cross-section may be constant or may vary along the length of the microchannel 16. Preferably the width of the channel is in the range of 50 to 500 μm and the dimension ratio between said depth and width is larger than 0.5, preferably larger than 0.8 in the sense of improved capillary action. It is noteworthy that when the channel 16 is carved homogeneously into the stent body 12, an approximately semicircular cross section is obtained in which the size ratio is only 0.5.

As shown in fig. 2, the height of the semicircular lower channel region 26, which is the base region in the stent body or matrix 12, formed by homogeneous etching can be increased by the structural layer 18, laterally delimiting the upper edge-open channel region 28, so that an overall higher dimensional ratio and thus a better capillary action can be achieved for the transport of fluids. For this purpose, the structural layer 18 should have a layer thickness of more than 50 μm, preferably a thickness of 200 to 500 μm.

The structural layer 18 is not applied as a preform to the stent body 12, but is applied as a permanent adherent coating by a previously intangible substance. For this purpose, a fluid coating material, in particular a photoresist 30 (English: "Photo-resist"), is specified. A thick film photoresist such as an epoxy based photoresist is particularly suitable for this.

In the embodiment of fig. 2, photoresist 30 is applied immediately after etching of lower region 26, so that complementary upper channel region 28 can additionally conduct fluid. For this purpose, it is advantageous to increase the hydrophilicity of the structural layer 18 by means of suitable additives or a corresponding paint component (lackzusammesetzung).

The water affinity of the channel walls can also be modified by the optional use of chemistry to the surface after the structure is formed.

As shown in the embodiment of fig. 3, the photoresist 30 used as a mask is not removed when etching the lower region 26 on the support body 12, but remains for an additional flow function. As shown, the open surface 32 facing the atmosphere can also be reduced by undercutting in addition to the raised channel walls, which can further improve capillary action. In principle, it is also conceivable that the undercut edge regions of the channels 16 can be produced as undercut structures of the carrier body 12 by selecting suitable etching parameters.

Fig. 4 shows an embodiment. In this exemplary embodiment, the structural layer 18 laterally delimits the microchannels 16 over the entire depth thereof, wherein a high dimensional ratio is achieved here by a corresponding layer thickness of the photoresist 30. In addition to the optoelectronic structuring of the channels 16 in the structural layer 18, the support body 12 can also be structured by a preceding (homogeneous) etching, for example the free etching piercing means 14.

Fig. 5 shows a method sequence for the optoelectronic structuring of the channels 16 on a previously etched carrier body structure. The support body 12 as substrate is first provided with a first photoresist layer 30' (fig. 5a, b). An ultraviolet exposure is then performed through a photo mask 32, wherein the photoresist 30' under the light-transmissive mask regions is polymerized or hardened, while the masked regions 34 are rinsed away after exposure and development (fig. 5c, d). The stent body 12 is then provided with an etching agent by means of the thus produced recesses 36 in the layer 30', wherein the channel regions 26 are homogeneously free-etched. After removal of the photoresist layer 30' (fig. 5f), channel elevations 28 are formed by further photo-structuring of the second thick-film layer 30 "by means of a mask 38, corresponding to the previously etched channel runs (fig. 5 i). The hardened photoresist remains permanently on the substrate 12 as a structural layer 18 and thus performs a fluid-directing function for improved fluid delivery.

The size ratio of the channels 16 is increased in the method flow shown in fig. 6 by a plurality of successive etching steps. The upper partial cross-section 40 of the channel 16 is formed in the support body 12 by a first etching, corresponding to the previous description in fig. 5a to f (fig. 6a to f). A deepened partial cross-section 42 is then produced in a second or further etching by at least one repetition of these steps, so that the channel 16 penetrates almost the entire stent body 12, but does not extend homogeneously in the width direction (fig. 6g to k). In principle, it is also possible to carry out a plurality of etching operations parallel to one another on both sides of the support body 12 until the channels 16 are completely etched through, wherein then at least the bottom side thereof must be closed, for example by applying a film.

Claims (23)

1. Microfluidic system for the removal of body fluids, having a carrier body (12) which is preferably provided with a piercing means (14), a semi-open microchannel (16) which is provided on the carrier body and serves for the capillary transport of the fluid from a removal position to a destination position (22, 24), characterized in that the carrier body (12) is coated for the transport of the fluid with a structural layer (18) which delimits the microchannel (16) laterally at least in an upper region.

2. The microfluidic system according to claim 1, wherein the microchannel (16) has a lower cross-sectional area (26) which is provided in the support body (12) and is preferably engraved, and an upper cross-sectional area (28) which is located thereon and is formed in the structural layer (18).

3. The microfluidic system of claim 1, wherein the structural layer (18) laterally bounds the microchannel (16) over the entire depth of the microchannel (16).

4. The microfluidic system according to any of claims 1 to 3, wherein the structural layer (18) is formed by a photoresist (30), preferably a thick film-photoresist.

5. The microfluidic system according to any of claims 1 to 4, wherein the structural layer (18) is structured optoelectrically in order to form or to increase the microchannels (16).

6. The microfluidic system according to any of claims 1 to 5, wherein the structural layer (18) has a layer thickness of more than 50 μm, preferably a layer thickness of 200 to 500 μm.

7. Microfluidic system for the removal of body fluids, with a holder body (12) preferably provided with a puncture mechanism (14), a semi-open microchannel (16) arranged on the holder body and serving to transport fluids from a removal site to a destination site (22, 24) in a capillary manner, characterized in that the microchannel (16) has a plurality of partial cross sections (40, 42) which are engraved into depth from the surface of the holder body (12) by successive etching steps.

8. The microfluidic system according to any of claims 1 to 7, wherein the dimensional ratio of the depth to the width of the microchannel (16) is greater than 0.5, preferably greater than 0.8.

9. The microfluidic system according to any of claims 1 to 8, wherein the microchannel (16) has a clear width in the range of 50 to 500 μm.

10. The microfluidic system of any one of claims 7 to 9, wherein the partial cross-section (40, 42) is formed by etching through a photochemical mask.

11. The microfluidic system according to any of claims 1 to 10, wherein the microchannel (16) has undercuts in the region of its longitudinal edges, preferably by means of bottom-side etching.

12. Microfluidic system for the removal of body fluids, having a carrier body (12), preferably provided with a piercing means (14), a semi-open microchannel (16) which is provided on the carrier body and serves for the capillary transport of a fluid from a removal position to a destination position (22, 24), characterized in that the microchannel (16) has undercuts in the region of its longitudinal edges, preferably formed by means of bottom-side etching.

13. The microfluidic system according to any of claims 1 to 12, wherein the support body (12) is made of a homogeneous etchable material.

14. The microfluidic system according to one of claims 1 to 13, wherein the carrier body (12) is preferably formed as a planar shaped part from metal, in particular from high-grade steel.

15. The microfluidic system according to any one of claims 1 to 14, wherein the support body (12) formed from a flat material has a thickness of 100 to 450 μm, preferably 150 to 300 μm.

16. The microfluidic system of any one of claims 1 to 15, wherein the structural layer (18) has an additional substance or component that increases hydrophilicity.

17. The microfluidic system of any one of claims 1 to 16, wherein the wettability of the walls of the microchannels (16) is increased by a chemical surface treatment.

18. The microfluidic system according to any of claims 1 to 17, wherein at least one partial structure of the support body (12), preferably the piercing means (14), is formed by etching or punching outside the microchannel region.

19. Disposable sampling element comprising a microfluidic system (10) according to any one of the preceding claims.

20. Use of a microfluidic system (10) according to any one of the preceding claims for transporting a sample fluid from a withdrawal site to a destination site (22, 24), in particular to a detection region.

21. A method for producing a microfluidic system for removing body fluids, in which method fluid-conducting and semi-open microchannels (16) are raised or formed by a photoresist layer, in particular a thick-film photoresist (30), applied to a carrier body (12).

22. A method according to claim 21, characterized in that the photoresist (30) is sputtered or scratched as a thick film onto the support body (12) or applied to the support body (12) by means of a dip coating.

23. A method as claimed in claim 21 or 22, characterized in that the microchannels (16) are cut into the support body (12) by mask etching the first photoresist layer (30'); and a second photoresist layer (30') is applied after the first photoresist layer is removed and is structured photoelectrically to increase the microchannels (16).