DE19846958C2 - Method for manufacturing a device for the transport of very small quantities of liquid - Google Patents

Description

The invention relates to methods for producing a device for transporting smallest amounts of liquid in which a system of microstructured Cavities that are at least partially channeled to the environment of a wearer are performed, is formed in the polymeric carrier in that microstructures in a first plate-shaped carrier part by a second plate-shaped carrier part are covered, between the materially identical plate-shaped carrier parts a connecting layer is introduced, the material composition is similar to that of the plate-shaped carrier parts.

The microstructured cavities are, for example, for microfluidic Applications in biotechnology are necessary where there is precise knowledge of an enclosed volume of liquid in the range of picoliters arrives. If the cavities are designed as microchannels, liquids can continuously transported electrokinetically or by pressure. Closed cavities are used to enclose precisely defined sample volumes uses and prevent the evaporation of the very small sample amounts. Comparable structures are also in the area of microfluidic displays necessary where colored liquids are precisely defined by microchannels Positions must be brought.

A variety of known technical solutions underlines that the Microstructuring of analytical instruments for the predominant use in the Medicine, biotechnology and pharmacology in significant in recent years Has gained in importance.

For the analyzes originally carried out in glass capillaries, in increasingly plate-shaped microfluidic components with it branching channel structures enforced. The channel structures were initially introduced into silicon wafers by etching, as used in semiconductor technology Manufacture of integrated circuits is known, we now want to move on to Use plastics. The motivation for using them is not just through the inexpensive manufacture determines, but also the advantageous Material properties such as optical transparency, biocompatibility and low Fluorescence in certain wavelength ranges.  

The introduced as liquids in the channels and at channel branches substances reacting with one another should be present in a continuous channel area optical means are analyzed. As defined for this purpose Cross-sectional dimensions for the channels in the range from previously 10 µm to 100 µm high demands are made on the production of such products posed.

So is from US 5 376 252 for a microfluidic device known, an elastic between two flat dimensionally stable base layers To lay interlayer, which is a microstructured made by molding Channel system contains.

Such a structure has the disadvantage that deformation of the elastic Intermediate layer affect the entire component. Dosing and Tightness problems are sequelae that negatively affect usability influence.

Another known solution in the form of an integrated device too electrophoretic purposes are described in US 5,770,029. The in essential device composed of two parts contains in one Base plate microstructures in the form of microchannels, for sealing one Cover plate is used. The microchannels contain an enrichment channel and a main electrophoretic flow path arranged so that Waste does not get into the main flow path, but the facility through a can leave separate outlet opening. As an economical variant for the Single use is suggested to make all components from plastic. Changes in the shape and cross-section of the channels are there described manufacturing technology to be expected if width and Depth dimensions in a size of 10 µm and smaller are required and if in particular the fluctuation range of these dimensions is less than 5% should.

Finally, it is known from DE 195 24 795 A1, adjacent to a channel a recess for receiving a connecting means in one of the the touching surfaces of the housing parts. It is also envisaged that to weld the two housing parts practically together by doing the same thing Material such as the housing parts existing connection means heated or heated in the recess is made.  

The disadvantage is that the two housing parts do not after joining on all adjoining contact surfaces by the connecting means are interconnected. This can lead to jumps in the material properties lead, even if the material of the connection means that of the housing parts equal. Influences through a spatial variation of physical Parameters such as B. refractive index, absorption coefficient and Thermal conductivity coefficients cannot be excluded.

Microfluidic displays are also becoming high Manufacturing technology requirements for the graphic display device placed, in accordance with the picture content at least two, in the Contrasting liquids in a meandering micro-channel structure are promoted by micropumps. After the pumps are switched off, it forms a stationary pattern consisting of liquid segments, which the Displays ad content. The decisive advantage for the user is that Availability of an alphanumeric display of good visibility with low Current consumption compared to LCD displays because the display in the steady state occurs without current. Is a change in the image content required, the old image content is replaced by the new image content and in pushed a separator, at the outputs of which the segregated liquids respective micropumps are available again.

The principle requires the use of optically transparent Plastic materials, with microchannels in the size of a few 10 µm. To one to achieve correct representation of the symbols by means of the two liquids to these microchannels special requirements in terms of accuracy and Reproducibility posed during manufacture. This applies in particular to the Reproducibility and constancy of the channel cross sections to the position of a Define liquid segments precisely, as well as an extremely low Surface roughness in order to keep the pressure drop in the microchannel as small as possible hold.

The object of the invention is to provide a method for the surface of plate-shaped bodies in their Connect the whole uniformly well without getting into the surfaces incorporated microstructured channels in shape and cross section influence.  

This task is accomplished in a method of the type mentioned by Features of the characterizing part of claim 1 solved. Advantageous configurations are given in claims 2 to 6.

With the method according to the invention, a carrier with a uniform, structure corresponding to a monolithic body, in that the Carrier made of plate-shaped carrier parts with a connecting layer is whose material composition in a solvent is that of plate-shaped carrier parts are similar. It is particularly important that the Thickness of the layer the width and depth dimensions of the microstructured Cavities significantly below. This keeps the microstructured Voids their, by hot stamping z. B. highly accurate under vacuum conditions generated parameters at. Edge rounding, material compression, bending and similar changes are excluded and so the flow behavior of the liquids filled into the cavities has a positive effect.

The fact that the layer in the dissolved state between the plate-shaped Carrier parts is introduced, this connects after the volatilization of the Solvent reactive with the surfaces of the two plate-shaped parts. Self No edge structure is observed at the connecting surfaces by electron microscopy recognize so that a carrier produced in this way except for the microstructured Cavities has the structure of a monolithic body. That affects particularly positive for the accuracy of measurements on enclosed samples, because the carrier has no foreign materials and no cracks in the Contains material properties. Influences by a spatial variation of physical parameters such as B. refractive index, absorption coefficient and Thermal conductivity coefficients are excluded.

The method is explained below with reference to the schematic drawing become.

The figure shows in the direction of the arrow the sequence in the manufacture of a device for Sample analysis in three steps, the presentation emphasizing the principle should and therefore by no means corresponds to the actual proportions.

According to the figure, the manufacture of the device according to the invention begins with the fact that in a first step a first polymeric, plate-shaped carrier part 1 with an impression tool 2 by hot stamping z. B. can be introduced under vacuum conditions microstructures 3 . The carrier part 1 consists of polymethyl methacrylate (PMMA). However, other materials, in particular thermoplastics such as. As polycarbonate (PC) or polyethylene (PE) can be used.

First, a structural negative of the desired microstructure 3 is produced from a very hard material, typically metal or silicon, using microtechnical methods. For example, a step from a method which is known under the name LIGA technology (LIGA process, Microelectron. Eng. 4 ( 1986 ) 35-56) is suitable for the production of metallic tools. A resist layer is exposed to synchrotron radiation using a mask in an X-ray lithographic process. For this purpose, a device can be used, for example, which is described in German patents DE 44 18 779 C1 and DE 44 24 274 C1. The shape that arises after the development of the resist is galvanically filled with the intended material, so that after the resist has been removed, the structure negative of the microstructure 3 is present as an impression tool 2 . For example, the known methods of wet chemical etching of silicon or surface processing with reactive ion etching are suitable for producing structure negatives from silicon.

Using an impression device for microsystem structures, e.g. B. according to DE 196 48 844 C1, the molding tool 2 is heated together with the polymeric carrier part 1 to a temperature above the glass transition temperature of the polymer material. The structures contained in the molding tool 2 are preferably transferred to the carrier part 1 under vacuum conditions in that the two parts are pressed against one another under high pressure. By cooling the carrier part 1 and the molding tool 2 while they are still in close contact to a temperature below the glass transition temperature of the polymer material, the structures in the carrier part 1 solidify. As a result, the microstructures 3 are retained after the impression tool has been removed. Of course, replication techniques such as. B. casting, UV reaction molding, injection molding or other embossing processes applicable.

A second carrier part 4 , which consists of the same polymeric material as the first carrier part 1 , serves to cover the microstructures 3 . Microstructured cavities 5 are created . At least some of the cavities 5 are connected to the environment via channels 6 , so that filling and emptying is ensured. The channels 6 can be incorporated according to the figure in the carrier part 4 or in another way, for. B. be guided laterally to the environment.

Between the two carrier parts 1 and 4 , a layer 7 is introduced to connect them in accordance with step 2 , which is in a solvent such as. B. methyl acetoacetate, contains only the material of the two support parts 1 and 4 . Under certain circumstances, it is also possible to use a polymer whose molecular structure only very closely resembles that of the two carrier parts 1 and 4 . The thickness of the layer 7 is of particular importance, since this has a decisive influence on the functionality of the microstructured cavities 5 . It is important to prevent layer material from entering the microstructures 3 , or, in particular, from their edge regions being attacked by the solvent. With channel cross sections from 10 × 10 µm to 40 × 40 µm, a layer thickness of less than 0.6 µm is required. In addition, a negative effect of capillary effects when joining the two carrier parts 1 and 4 is to be avoided. Finally, it is important that the layer 7 have a uniform distribution over the entire connecting surface. If the layer material were to accumulate in the area of the channels 6 , this would otherwise penetrate into the microstructures 3 . For this reason, the channels 6 contained in the carrier part 4 , which is preferably to be coated, are temporarily closed by suitably worked pins, as a result of which a sufficiently closed surface is created. The layer 7 is applied after a cleaning process, in which the carrier part 1 is also included. Particles adhering to the surfaces, which destroy the homogeneity of the layer 7 and thus would prevent a complete connection of the workpieces involved, can thereby be removed to a sufficient extent.

The surface of the second carrier part 4 is first centered with a small amount of the dissolved polymer material in the order of a few microliters, e.g. B. provided by pipetting. The required layer thickness is then set by rapid rotation of the carrier part 4 fastened on a turntable, for which the viscosity of the dissolved polymer material and the rotational speed are mainly decisive. If, for example, the microstructured cavities 5 in a PMMA carrier are to have width and height dimensions in the range of 10 μm, the number of revolutions is several thousand revolutions per minute (4000-6000 rpm) with a solvent ratio of 1: 7-1: 11 PMMA required for the solvent methyl acetoacetate. The thickness of the layer 7 achieved under these conditions reaches the above-mentioned range and thus significantly falls below the width and height dimensions of the microstructured cavities 5 . Immediately after the layer 7 has been applied, both carrier parts 1 and 4 are connected to one another by mechanical contact, so that the microstructures 3 are delimited in a sealed manner by the carrier part 4 . Tilting errors should be excluded, lateral misalignment prevented and even pressure conditions guaranteed. This can be done, for example, in a suitable device in which the two carrier parts 1 and 4 can be placed on one another with a precise fit and without lateral play and can be subjected to a uniform force by means of a stamp. Alternatively, the connection can also be made by a rolling step. For a permanent and homogeneous connection, quick assembly within 20-60 s is particularly important to prevent the solvent from evaporating prematurely. Otherwise a defined and long-term stable connection of both workpieces would be more or less impaired. Then the solvent evaporates at room temperature. Of course, the processing time can be shortened by increasing the temperature or by using a drying oven with or without vacuum support.

The final structure of a monolithic body 8 is formed in a third step in that the compounds broken up by the solvent in the surfaces are formed again when the solvent evaporates, the molecules in the region of a boundary layer on each surface with the molecules of the layer 7 commitments.

After the solvent has evaporated, a uniform carrier is formed, which is only consists of one material and there are no discontinuities in the material properties the initially existing boundary layer of the surfaces involved.

The introduction of the connecting layer is not limited to this described method, although particularly good results can be achieved. In particular, rolling is also a very suitable method.

Claims (6)

1. A method for producing a device for transporting the smallest amounts of liquid, in which a system of microstructured cavities, which are at least partially guided through channels to the environment of a carrier, is formed in the polymeric carrier in that microstructures in a first plate-shaped carrier part are covered by a second plate-shaped carrier part, a connecting layer being introduced between the materially identical plate-shaped carrier parts, the material composition of which is identical to that of the plate-shaped carrier parts, characterized in that the connecting layer ( 7 ) has a layer thickness on the second carrier part ( 4 ) is applied, which substantially falls below the width and depth dimensions of the microstructured cavities ( 5 ), the material composition of the connecting layer ( 7 ) in a solvent of the material composition of the first and the second T rägerteils (1, 4) is similar, and wherein after the joining together of the support parts (1, 4), evaporate the solvent, after which the material composition of the interconnecting layer (7) of the material composition of the two carrier parts (1, 4) is similar. 2. The method according to claim 1, characterized in that in the second carrier part ( 4 ) existing channels ( 6 ) are closed before the application of the connecting layer ( 7 ), so that a sufficiently closed surface is formed for the coating. 3. The method according to claim 2, characterized in that the surface is subjected to a cleaning process before the coating to ensure a complete connection of the carrier parts ( 1 , 4 ). 4. The method according to claim 3, characterized in that the connecting layer ( 7 ) is applied as a polymer material in dissolved form and in an amount of a few microliters to the sufficiently closed surface, the adjustment of the layer thickness by rotation of the carrier part fastened on a turntable ( 4 ) is done. 5. The method according to claim 4, characterized in that for the carrier parts thermoplastic material is used. 6. The method according to claim 5, characterized in that the microstructured cavities ( 5 ) are formed by hot stamping under vacuum conditions in the plate-shaped carrier part ( 1 ).