EP3965930A1

EP3965930A1 - Microfluidic array, method of manufacture, measuring system comprising the microfluidic array, and use

Info

Publication number: EP3965930A1
Application number: EP20711846.4A
Authority: EP
Inventors: Sabine Ziemba; Michael Scharfenberg; Violetta Olszowka; Martina Schmidt; Juri Attner; Markus Bigler; Sascha Mario Epp; Martin Richner; Maria Bauer; Gottfried Reiter; Georg Bauer
Original assignee: Stratec Consumables GmbH; OVD Kinegram AG; Leonhard Kurz Stiftung and Co KG
Current assignee: Stratec Consumables GmbH; OVD Kinegram AG; Leonhard Kurz Stiftung and Co KG
Priority date: 2019-05-10
Filing date: 2020-03-11
Publication date: 2022-03-16
Also published as: US20220241781A1; JP2022531956A; WO2020229016A1

Abstract

The invention relates to a microfluidic array, a method for manufacturing same, a measuring system comprising the microfluidic array, and a use thereof.

Description

Microfluidic arrangement, method for its production and measuring system comprising the microfluidic arrangement and use

The present invention relates to a microfluidic arrangement, a method for its production, a measuring system comprising the microfluidic arrangement and a use.

In chemical analysis as well as in medical diagnostics, more and more systems are being developed that replace and expand classic laboratory analysis by integrating the individual process steps in microfluidic systems.

This development is particularly encouraged by the development of many new manufacturing processes, such as Thick lacquer processes or LIGA (lithography and galvanic impression), the new possibilities of combining

microfluidic structures opened.

Microfluidic systems are called lab-chips, lab-on-chip or pTAS (picro-total-analysis-systems). By reducing the size of the analysis systems, e.g. an on-site application can be implemented, for example the

Carrying out biochemical analyzes such as immunoassays, molecular diagnostic assays or cellular analyzes or the like in the form of a microfluidic system enable broad and inexpensive application. In particular, the analysis to be carried out directly from whole blood on site expands the application of such analyzes and offers great advantages for the patient as well as possibilities for reducing costs. An immunoassay is a detection method for biologically active substances (antigens / antibodies) that is frequently used in medical diagnostics; in molecular diagnostic detection methods, nucleic acids are detected; in cytometric methods, the cells in a sample

characterized.

Known microfluidic systems often include chamber systems with pump and / or capillary action, which consist of an essentially two-part laminate.

In a known embodiment, a “rigid”, often injection molded

Lower part on support structures that enable the investigation of liquids and their components. An upper part is arranged thereon, which e.g. a likewise “rigid” injection-molded upper part or, alternatively, a flexible film. The film or the rigid upper part does not have any structures and essentially acts as a cover. The support structures serve primarily as

Spacers so that the examination chamber has an exactly defined height, which is necessary, for example, for the non-overlapping introduction of blood cells into a microfluidic chamber. If a flexible film is used as the upper part, possible differences in flatness of the lower part can also be compensated for due to the flexibility of the film used.

With the methods known from the prior art for the production of microfluidic arrangements, any desired structures with high aspect ratios can be produced by injection molding, but there are also other technical disadvantages in addition to the highly process-dependent costs.

For example, components with a wall thickness of less than 500 μm are very difficult to produce, which makes the application e.g. limited by confocal reading, since an optical thickness of less than 175 μm is a prerequisite for the use of standard optics. Newer optical methods aim at even lower ones

Distance between the optics and the sample in order to also capture phenomena from the optical near field. Wall thicknesses of less than 10 μm are advantageous for this. Furthermore, the two-dimensional demolding of an injection molded part from the injection mold over larger areas generates high forces which are difficult to control, especially when demanding flatness of the injection molded part is to be guaranteed.

Modifications to the injection-molded parts, such as additional steaming, printing, etc. must always be carried out on individual parts, which can only be achieved through complex, cost-intensive and slow processes.

In addition, thin-walled injection molded parts often do not show what they want

Dimensional stability, but tend not to be flat enough

Twists and / or delay.

It is therefore the object of the present invention to provide an improved method for producing a microfluidic arrangement which enables a microfluidic system to be provided in a simple and cost-effective manner.

The object of the present invention is achieved by providing a method according to claim 1 for producing a microfluidic arrangement comprising at least one, at least partially completely covered flow channel in fluid connection with at least one inlet and at least one outlet, the method comprising the following steps:

a) providing at least one base layer,

b) providing at least one flexible cover layer, the at least one

Structural element which is arranged on a surface of at least one side of the cover layer comprises, and

c) Arranging the at least one flexible cover layer on at least a partial area of the at least one base layer, so that on at least one

Part of the, on the surface of at least one side of the cover layer

arranged at least one structural element is arranged at least a partial area of the at least one base layer with at least partial formation of at least one, at least partially completely covered flow channel. Preferred embodiments of the method according to the invention are disclosed in the dependent claims 2 to 33.

The object of the present invention is also achieved by the

Provision of a microfluidic arrangement according to claim 34 comprising at least one, at least partially completely covered

Flow channel in fluid connection with at least one inlet and at least one outlet, preferably produced by a method according to one of claims 1 to 33, wherein the microfluidic arrangement is characterized in that the microfluidic arrangement comprises at least one base layer and at least one flexible cover layer comprising at least one comprises structural element arranged on a surface of at least one side of the cover layer, with at least one structural element arranged on at least one partial area of the at least one structural element arranged on the surface of at least one side of the cover layer

Partial area of the at least one base layer with at least partial formation of the at least one, at least partially completely covered

Flow channel is arranged.

Preferred embodiments of the microfluidic arrangement according to the invention are disclosed in the dependent claims 35 to 63.

The object of the present invention is also achieved by the

Provision of a measuring system according to claim 64 comprising at least one microfluidic arrangement according to one of claims 34 to 63 and at least one detector.

Preferred embodiments of the measuring system according to the invention are disclosed in the dependent claim 65.

The object of the present invention is also achieved by the

Providing a use according to claim 66 of a microfluidic

Arrangement according to one of Claims 34 to 63 or a measuring system according to one of Claims 64 or 65 in the in-vitro examination of human or animal body fluids, in particular in the in-vitro blood analysis. A microfluidic arrangement according to the invention comprises at least one, at least partially completely covered flow channel in

Fluid connection with at least one inlet and at least one outlet, wherein the flow channel preferably has a capillary effect on applied and / or introduced liquids.

The flow channel thus preferably has a capillary activity, which is further preferred for the transport of liquids within the microfluidic

Arrangement can be used.

The at least one flow channel is in fluid connection with at least one inlet and at least one outlet, wherein a liquid to be examined is preferably applied or introduced into the microfluidic arrangement according to the invention via at least one inlet and wherein preferably air that flows through during the transport of the liquid to be examined the at least one flow channel is displaced via the at least one outlet

can escape.

The at least one flow channel produced by the method according to the invention preferably has a flow channel according to the invention

microfluidic arrangement a height of at most 500 pm, preferably from a range from 0.1 pm to 500 pm, preferably from a range from 0.15 pm to 270 pm, preferably from a range from 0.2 pm to 170 pm,

preferably from a range from 0.5 pm to 100 pm, more preferably from a range from 0.65 pm to 75 pm, further preferably from a range from 0.75 pm to 55 pm, further preferably from a range of 0.85 pm to 35 pm, more preferably from a range from 0.95 pm to 20 pm, in particular from a range from 1 pm to 10 pm. Such a flow channel is preferably a capillary-active flow channel.

The inventors have found that it is possible by means of the method according to the invention to provide a microfluidic arrangement that has a low Has wall thickness and still has sufficient stability of the provided capillary-active structures of the microfluidic arrangement.

A microfluidic arrangement according to the invention preferably has at least one base layer and at least one cover layer arranged thereon, the at least one base layer further preferably not having any structural elements, preferably capillary-active channels and chambers formed at least in part from structural elements.

Those contained in a microfluidic arrangement according to the invention

Structural elements such as capillary-active channels and / or capillary-active chambers and / or at least partially formed from structural elements

Spacers and / or inlet elements and / or outlet elements are

preferably arranged at least partially in and / or on the at least one cover layer and / or on a surface of the at least one cover layer.

In particular, the capillary-active channels and / or capillary-active chambers are preferably only created when the base layer and cover layer are brought together.

The at least one cover layer which is used to produce a microfluidic arrangement according to the invention in the method according to the invention comprises at least one structural element which is arranged on a surface of at least one side of the cover layer.

The term “at least one structural element” is preferably understood to mean at least one depression and / or at least one raised element which is arranged on a surface of one side of the cover layer, preferably the cover layer.

A recess can be designed as a channel and / or as a chamber.

A raised element preferably has a, preferably planar, base area which is arranged on the surface of one side of the cover layer, preferably the cover layer, and which is preferably oval or angular. A raised element can for example be designed as a convex body or as part thereof his. For example, a raised element can be designed independently of one another as a spherical segment, pyramid, cone, cylinder, prism, prismatoid, spherical layer, truncated cone, irregularly shaped body or combinations thereof.

A raised element preferably has a top surface which is arranged opposite the base area, preferably parallel to the base area and which is congruent or incongruent to the base area.

After arranging the at least one flexible cover layer on at least one

The at least one sub-area of the at least one base layer is spaced apart

Structural element preferably the at least one flexible cover layer and the at least one base layer with formation of at least one, at least

partially completely covered flow channel. The distance between the base and top layers can be greater than the height of the structural element in the unfilled state, possibly also only locally.

When filling the flow channel with at least one liquid and / or

Dispersion, preferably suspension and / or emulsion, each at least one under standard conditions (for example pressure 1013 mbar, temperature: 25 ° C) and / or also at elevated temperatures and / or elevated or lower pressure (for example pressure between 900 mbar and 1100 mbar , Temperature: 50 ° C) has liquid phase, the at least one flexible cover layer, preferably by the resulting capillary forces, in particular by suction forces and / or by pressure forces on the at least one base layer, so that preferably the height of the at least a flow channel

adjusts according to the respective height of the at least one structural element. This also offers the advantage that the exact height of the at least one flow channel can preferably be determined with knowledge of the dimensions of the structural elements which are in direct contact with the opposite layer.

Liquid and / or dispersion, preferably suspension and / or emulsion, is preferably a flowable medium with a dynamic viscosity of less than 1000 mPas, preferably less than 100 mPas, particularly preferably smaller understood as 50 mPas. The viscosity data are preferably based on a temperature range between approx. 20 ° C and approx. 50 ° C. The dynamic viscosity is measured in each case, preferably under standard conditions, with a rotary viscometer in accordance with the DIN EN ISO 2555: 2018-09 (Plastics - Resins in the liquid state, as emulsions or dispersions - Determination of the apparent viscosity with a rotary viscometer with a single cylinder (ISO 2555: 2018); German version of EN ISO 2555: 2018 - date of issue: 2018-9). In this case, a defined, controlled rotating body is preferably immersed in the correspondingly tempered medium to be measured and the resistance of the medium is determined, in particular at different speeds and / or temperatures.

Such liquids and / or dispersions can be, for example, human or animal body fluids such as blood, sweat, tears, lymph, saliva, sputum, gastric juice, secretions of the pancreas, bile, urine, sperm,

Amniotic fluid, aqueous humor, breast milk, synovial fluid,

Cerospinal fluid, bone marrow aspirate, or mixtures thereof.

Such liquids can, for example, also be dispersions or

Be suspensions or solutions.

The height of the at least one flow channel is preferably one

microfluidic arrangement according to the invention of at most 500 pm,

preferably from a range from 0.1 pm to 500 pm, preferably from a range from 0.15 pm to 270 pm, preferably from a range from 0.2 pm to 170 pm, preferably from a range from 0.5 pm to 100 pm pm, more preferably from a range from 0.65 pm to 75 pm, more preferably from a range from 0.75 pm to 55 pm, more preferably from a range from 0.85 pm to 35 pm, more preferably from a range from 0.95 pm to 20 pm, in particular from a range from 1 pm to 10 pm, at least partially from the at least one

Structural element provided.

When the chamber is filled, the at least one flexible cover layer is “sucked” onto the at least one base layer by the capillary pressure. Here comes that at least one structural element in direct contact with the base layer. This furthermore preferably leads to a changed brightness of the at least one structural element in transmitted light. Before direct contact, there was air or another medium with a different material than the material of the at least one structural element

Refraction indices between the at least one structural element and the

Base layer, whereby the at least one structural element appears in transmitted light as a light area in the form of the cross section of the at least one structural element. In the case of direct contact with the base layer, the at least one structural element preferably appears darker in transmitted light than without this contact, because more preferably an optically effective interface is now no longer present or only insignificantly present.

The term “in transmitted light” preferably means passing through

electromagnetic radiation, preferably with a wavelength from a range from 300 nm to 800 nm, preferably 380 nm to 750 nm, through at least partial areas of the microfluidic arrangement, preferably through at least

Sub-regions of the at least one base layer and one arranged thereon

Top layer, understood. It is also possible to use UV light (UV = ultraviolet) and IR light (IR = infrared), more preferably in combination with up and / or down converters (luminescence, phosphorescence, etc.) or

Camera systems (UV-IR sensitive).

This change in the brightness of the at least one structural element in transmitted light can serve as a reference or as a measuring element as to whether the desired distance between the at least one flexible cover layer and the at least one

Base position, which preferably corresponds to the height of the at least one structural element, has set.

For an advantageous corresponding optical measurement or detection this

At least one specially shaped structural element with which this optical measurement or detection can be carried out particularly easily and / or reliably can be provided for the change in brightness or this desired distance.

For example, at least one particular cross-sectional shape and / or at least one particular cross-sectional size is possible. At least one in Structural element finely graduated in height, so that a graduated change in brightness can preferably be detected optically or metrologically, for example by means of at least one appropriately arranged sensor. The positions of the structural elements can also be determined so that they can be incorporated into the image evaluation.

The at least one structural element can be produced using methods known from the prior art, for example by thermal replication, i. E. Introduction of the structures into a thermoplastic lacquer by means of a heated embossing tool and / or UV replication, i.e. Introducing the structures into a liquid or gel-like lacquer under irradiation with UV radiation while the lacquer is in contact with an embossing tool, and / or laser structuring, i.e. Ablation of the structures in a plastic, and / or photolithography, i.e.

Exposure of a photoresist by means of radiation through a mask, subsequent development and washing of the photoresist with formation of the structures, and / or mechanical structuring or processing.

The at least one cover layer, preferably cover layer, preferably has at least one analysis element.

The at least one analysis element preferably has all the structural elements required for later use, for example at least parts of a flow channel formed from at least one structural element and / or chamber formed from at least one structural element, each of which is preferably in fluid communication with at least one inlet in the microfluidic arrangement according to the invention and can stand at least one outlet.

The at least one cover layer preferably has defined optical and / or mechanical properties at least in the area of the at least one analysis element, for example with regard to the thickness of the at least one cover layer and / or the height of the at least one flow channel and / or its width. The geometric structures present in the at least one analysis element preferably have a defined height, which preferably together with the base layer form a defined volume that is in the microfluidic arrangement according to the invention for the analysis and / or quantification in particular of components of a liquid to be examined and / or dispersion, preferably human or animal body fluid, for example of blood cells in blood.

The at least one analysis element can preferably comprise at least one inlet and / or at least one outlet, each of which is in fluid connection with the at least one flow channel. Alternatively, the at least one flow channel of the at least one analysis element can also be in fluid connection with the at least one inlet and / or the at least one outlet of the microfluidic arrangement according to the invention via at least one further flow channel.

The fluid connection between the at least one inlet and / or the at least outlet is preferably provided in step c) of the method according to the invention.

For example, the at least one base layer can have at least one inlet and / or at least one outlet which are brought into fluid connection with the at least one flow channel after the at least one base layer has been arranged on the at least one cover layer.

By arranging the at least one cover layer with the structures of the at least one analysis element on at least a partial area of the at least one base layer, at least one flow channel that is completely covered at least in areas is preferably formed.

The at least one analysis element, preferably the at least one

The flow channel of the at least one analysis element preferably has at least one structural element and optionally, for example, at least one surface texture and / or at least one outer edge.

A structural element of the at least one flow channel can for example be designed in the form of an elevation, for example as one at the end of the at least one stop edge arranged transversely to the flow direction. A stop edge can, for example, have a height of 10 nm to 500 nm, preferably 10 nm to 200 nm, and result in the liquid not running over the edge of the stop edge. This has the advantage that from the

Flow channel the liquid can not emerge in an uncontrolled manner, which brings advantages in the practical handling of the arrangement with it.

A surface texture can, for example, have a roughness of at least one

Be the surface of the at least one flow channel, in particular one

Roughness of Ra less than 1 pm, preferably Ra less than 0.1 pm, particularly preferably Ra less than 0.05 pm. This roughness is particularly advantageous when the at least one flow channel has a height of less than 500 μm, preferably less than 20 μm.

For example, in the method according to the invention, by selecting a suitable width and / or height and / or length of the at least one

Structural element, the width and / or height and / or length of the at least one flow channel of the microfluidic arrangement can be determined.

The at least one structural element, preferably at least one depression, for example at least one channel and / or the at least one chamber and / or at least one elevation, preferably has a height of at most 500 μm, preferably from a range from 0.1 μm to 500 μm , preferably from a range from 0.15 pm to 270 pm, preferably from a range from 0.2 pm to 170 pm, preferably from a range from 0.5 pm to 100 pm, more preferably from a range from 0.65 pm to 75 pm, more preferably from a range from 0.75 pm to 55 pm, more preferably from a range from 0.85 pm to 35 pm, more preferably from a range from 0.95 pm to 20 pm, in particular from a range from 1 pm to 10 pm.

A raised element can for example be designed as a convex body or part thereof. For example, a raised element can be independently of one another as a spherical segment, pyramid, cone, cylinder, prism, prismatoid, Spherical layer, tapered cone, irregular body or a combination thereof.

At least one structural element can furthermore be arranged inside the at least one flow channel, which is preferably designed in the form of a raised element and more preferably one, preferably planar, arranged on the surface of one side of the at least one flow channel

Has base which is preferably oval or angular.

The at least one structural element arranged in the flow channel is furthermore preferably selected from columns, hemispheres and combinations thereof. In supervision, i.e. In the cross-section of the structural element, the at least one column can have the following shapes: round, oval, angular, more preferably three or more corners, with sides of the same length or different lengths, star-shaped, etc., as well as irregular shapes.

The side surfaces of the at least one structural element can be flat and / or curved and / or perpendicular and / or inclined and / or a combination thereof, independently of one another.

The at least one structural element can be oriented differently to the flow direction. For example, a structural element can be designed as an elongated column (in plan view), preferably oriented in the direction of flow of the fluid to be examined through the at least one analysis element. Within at least one flow channel, several structural elements can also be designed as spacers with different shapes.

A suitable structural element is preferably used as a spacer

Maintaining the height of the at least one flow channel. In addition, by choosing a suitable structural element, Flows and / or eddies within the at least one flow channel can be controlled, for example promoted or suppressed.

Alternatively or additionally, a suitable structural element can be designed as a filter element, for example for filtering particles that are too large. In addition, structures can also form a filter area in which e.g. larger cells are separated off before the analysis or cells of different sizes are detected and / or analyzed in different local areas.

A structural element designed as a filter element preferably has

at least one side surface has at least one passage, at least one pore or a combination thereof, each of which is designed for the passage of fluid, preferably liquid, and / or of particles through the filter element

Allow structural element.

For example, at least one suitable structural element can also serve as a carrier for one or more suitable detection molecules, for example antibodies, which are present on at least partial areas of the surface of the corresponding

Structural element can be arranged

The at least one analysis element therefore preferably has the corresponding at least one geometric structure element.

The corresponding at least one geometric structural element of the

Analysis element can for example be arranged in at least partial areas of the at least one analysis element before the application of the at least one cover layer on the at least one base layer.

The method according to the invention therefore makes it possible in a simple manner to identify specific partial areas of the at least one analysis element by suitable measures, preferably by applying at least one suitable

Modifying element, for example in the form of a layer, to modify at least a portion of the surface of the at least one analysis element. As an alternative or in addition to applying modifying elements to the analysis element, modifying elements can also be or be applied to the base layer. In particular, it is also possible to apply one or more modification elements to the analysis element and to apply further modification elements to the base layer. This is preferred, for example, in the case in which the application of several layers of

Modifying elements on top of each other is or could be technically problematic and / or unfavorable, or in the case in which different types of

Modifying elements are to be kept separate before the flow channel is filled, so that they can only react with one another after filling and dissolving one or both of the modifying elements in the liquid to be examined.

Depending on the configuration of the at least one modification element, the physical properties, preferably the optical and / or the electrical and / or the mechanical properties, and / or the chemical properties of the surface of the at least one structural element and / or flow channel can be influenced.

For example, by choosing suitable modifying elements, the

Binding ability of at least partial areas of the surface of the at least one channel can be influenced, for example by applying suitable antibodies, antigens and / or in each case biologically active fragments thereof.

It is also possible, for example, to modify the hydrophobic and / or hydrophilic property by applying suitable molecules, for example water repellants.

The modification elements can be applied by at least partial vapor deposition and / or sputtering and / or spraying and / or printing processes and / or immersion processes. Both inorganic materials or organic materials or combinations thereof can be applied in one or more layers, it being possible for the individual layers to have materials that are different from one another or else the same. Local spraying can, for example, by prior covering with a mask layer. For this purpose, a mask with openings is applied precisely to parts of the analysis element and then the parts that are not covered are modified by spraying with modification elements, in particular a reagent.

The at least one flow channel can, for example, furthermore have constrictions and / or widenings of the cross section, for example by the

To control the flow rate of a liquid to be analyzed.

Suitable modification elements can be arranged, for example, as an additive in the at least one cover layer. Suitable additives can preferably emerge from the at least one cover layer, for example by diffusion and / or migration.

The at least one flexible cover layer preferably comprises, preferably

Cover layer, and / or the at least one base layer, preferably base layer, at least one additive, which is preferably selected from the group consisting of dyes and / or reagents that react with other components to form dyes or react with other dyes already present that the color is reduced, contrast media, stabilizers, light stabilizers,

Antioxidants, biological adjuvants, surfactants, and mixtures thereof. Dyes are understood in particular to be those substances which, in the range of UV radiation, visible light and IR radiation, have an optical

develop a noticeable effect.

If several additives are used in a microfluidic arrangement, then these can be applied in several layers overlapping one another and / or adjacent to one another and / or also as single-layer or multi-layer mixtures. The surface areas with side by side

Additives can, in particular, each have a different shape

Structural elements are combined, which provide different volumes in particular for the different additives. For example, differently shaped depressions can be arranged for different additives, in which the additives are then introduced. Depending on the type of additive, the volumes of the depressions can then be of different sizes.

The at least one additive is further preferably arranged in a releasable manner in and / or on the cover layer, preferably cover layer, preferably on or on at least partial areas of at least one surface of the at least one structural element and / or cover layer.

The at least one additive is more preferably soluble in and / or on at least partial areas of at least one surface of the base layer, preferably

Base layer, arranged. For example, the at least one additive can be arranged releasably in and / or on at least partial areas of at least one surface of the base layer, preferably the base layer, and at least one further additive can be releasably arranged in and / or on at least partial areas of a surface of a second cover layer, preferably a second cover layer, and / or preferably in and / or on at least partial areas of a surface of a second base layer, preferably a second base layer.

If several, preferably different, additives are to be arranged in the microfluidic arrangement, which can react with one another during storage and / or which diffuse out and / or dissolve and / or behave differently when flowing in, it can be preferred to use at least one of the To apply additives to the base layer via a printing process and to introduce at least one further additive into the flexible layer, preferably into the cover layer, more preferably into the cover layer, using the processes described above.

If the processes described above are to be used to produce flow cells and / or cuvettes which are not filled with capillary action, but instead are filled and pressurized, it can be advantageous to have a flexible layer on the

The structural layer and / or the side facing away from the cover layer is drawn up on a base layer and connected to a second rigid layer, in particular glued and / or bonded or pressed by means of a holder. If, in turn, several additives are to be introduced into a flow cell and / or cuvette, which is filled or acted upon with pressure, it can be advantageous to apply a first flexible layer on a first base layer on the side facing away from the structure layer and / or the cover layer and on a second

Base layer a second flexible layer on top of the structural layer and / or the

Apply cover layer facing away from the side and then the two

to connect the resulting laminates to the structure sides,

in particular to be glued and / or connected or pressed by means of a holder.

More preferably, the at least one additive is microencapsulated in particles which are arranged in and / or on the top layer, preferably top layer, preferably on or on at least partial areas of at least one surface of the at least one structural element and / or top layer.

If the at least one additive is arranged in the cover layer, the at least one additive can in particular be introduced by an extrusion process.

Additives that are otherwise difficult to dissolve can also be introduced into the top layer by means of extrusion.

The at least one additive can be arranged in at least one chamber, which is preferably in fluid communication with the at least one channel, and / or in at least one lacquer layer, the at least one lacquer layer preferably being arranged on at least partial areas of at least one surface of the at least one channel.

The at least one additive can be arranged in at least one depression, which is preferably in fluid connection with the at least one channel, and / or in at least one lacquer layer, the at least one lacquer layer preferably being arranged on at least partial areas of at least one surface of the at least one channel.

The aforementioned additives are preferably at least partially included in the

examining liquid released, for example, in the liquid Particles contained, for example cells, to modify, for example to stain, and / or to enable a specific detection reaction.

The aforementioned modification elements preferably remain, for example

Layers, bound on the applied surface.

The aforementioned additives can preferably diffuse into the fluid to be examined, preferably liquid.

By modification, in particular by covering the modifying elements, in particular partial areas of the modifying elements, with suitable ones

Materials, the rate of dissolution and / or the diffusion rate for the delayed release of modifying elements, in particular reagents, into the liquid to be examined can be controlled. This can be one or more modifiers, in particular reagents, whose dissolution rate and / or diffusion rate is preferably the same or different and / or is delayed differently.

The geometric configuration of the at least one

Structural element and thus the flow channel formed, for example by choosing suitable slopes, influenced.

Preferably, at least one structural element in each case comprises at least one base area and in each case at least one first side surface directly connected to the base area, the angle between the at least one

Base area and the at least one first side area is from 30 ° to 90 °, preferably from 45 ° to 90 °, particularly preferably from 70 ° to 90 °.

For example, the at least one flow channel can be designed as at least one chamber, at least in some areas.

A chamber preferably has a defined volume that leads to a

Storage of a defined amount of liquid over a defined period is suitable. Due to the defined volume of the chamber, there is also the volume the amount of liquid contained therein is known relatively precisely when the chamber is almost completely full. For example, a chamber can be used as a

Storage container for reagents, for example the aforementioned additives, be formed.

If the chamber is partially filled in the direction of flow, the

Amount of liquid in the chamber by determining the filled area, e.g. by taking an image with subsequent evaluation.

The at least one analysis element can preferably further comprise at least one functional element which is arranged at least in fluid communication with the at least one channel and is preferably selected from the group consisting of microfluidic separators, microfluidic mixers, microfluidic pumps, microfluidic valves, and combinations thereof .

The at least one analysis element can preferably further comprise at least one optical element, preferably from the group of optical lenses, preferably microlenses, diffractive elements, moiré elements, registration marks and combinations of the aforementioned elements.

The flow channel can have one or more chambers, wherein

in particular an antechamber and a main chamber are provided, in which the antechamber can serve as a mixing chamber in which, for example

Modifying elements can be mixed.

Furthermore, at least one antechamber and / or at least one

Post-chamber can be arranged in the at least one analysis element, which are preferably in fluid communication with the at least one main chamber.

The aforementioned functional elements can preferably also be used to control the movement, mixing, separation and / or other process steps within the at least one flow channel of the microfluidic arrangement. Preferably, at least one liquid can be moved, mixed, separated and / or otherwise processed in at least one flow channel produced by the method according to the invention.

Preferably in at least one, more preferably by the

Process according to the invention produced, flow channel liquids and / or dispersions, preferably suspensions and / or emulsions, each at least one under standard conditions (for example pressure 1013 mbar, temperature: 25 ° C) and / or also at elevated temperatures and / or elevated or lower pressure (for example pressure between 900 mbar and 1100 mbar, temperature: 50 ° C.) have liquid phase, are moved, mixed, separated and / or otherwise processed.

Suitable suspensions are, for example, biological fluids which can contain cells of the most varied of origins. The cells contained in a biological fluid are, for example, not only limited to the body's own cells, such as erythrocytes, leukocytes or platelets, but also include cells foreign to the body, for example pathogens such as bacteria, viruses, algae, parasites, fungi or protozoa.

Preferably in at least one, more preferably by the

According to the method produced, flow channel at least one liquid and / or dispersion, preferably suspension and / or emulsion, which has at least one liquid phase under standard conditions (pressure 1013 mbar, temperature: 25 ° C), with at least one additive, for example, a specific detection allowed, for example a specific pathogen, to be contacted and then preferably by an optical one

Evaluation method, preferably in a measuring system according to the invention, analyzed and / or quantified.

The functional element can preferably contain a material that absorbs liquids, for example cellulose fibers, in order, for example, to prevent liquids from escaping unintentionally. A quantification can be done, for example, by counting a number of particles, for example the number of cells, and / or by comparing a coloration with one from a

The calibration curve obtained from the dilution series can be carried out by methods known to those skilled in the art. The coloration can be determined locally or it can be determined integrally over the entire sample. This means that an internal standard can be applied with almost no additional costs.

A measuring system according to the invention comprising at least one microfluidic arrangement according to one of claims 35 to 62 and at least one detector, for example at least one planar radiation detector, such as a photocell, an image chip or a photomultiplier.

In addition, the measuring system can also have optical microscopes or magnifying glasses, e.g. to be able to control the filling of the cells by operating personnel and / or also to enable certain evaluations by operating personnel.

A measuring system according to the invention preferably further comprises at least one radiation source. A radiation source is one

Emission source that generates electromagnetic radiation at one or more discrete wavelengths or over a specific spectrum with a specific, possibly wavelength-dependent intensity. It includes the areas of electromagnetic radiation UV, visual area; IR. Several, identical or different radiation sources are also preferably used.

The at least one microfluidic arrangement can be arranged in a measuring system according to the invention for single and / or multiple use.

Different analyzes are preferably carried out by a measuring system. For example, a measuring system can be used to determine the number of cells and / or their shape in a sample, or to determine a quantitative

Perform fluorescence measurement and / or to characterize cells, for example to differentiate between different cell types, their cell cycle and any degeneracies. In a preferred embodiment, the at least one flexible cover layer has a maximum thickness of at most 250 gm, preferably at most 100 gm.

More preferably, the at least one flexible cover layer comprises at least one polymer, which is preferably selected from the group consisting of thermoplastics, thermosets and thermoplastic elastomers (TPE), preferably PET, PMMA, ABS, PEN, BOPP, PVC, PA, particularly preferably PET or PEN and mixtures thereof is selected.

By selecting suitable components of the flexible cover layer and its thickness, in particular the optical properties of the cover layer can be matched to an intended use, for example by adapting the optical properties such as transparency and / or absorption of the cover layer to the analysis system to be used, for example.

Preferably, the at least one flexible cover layer is at least regionally, preferably in an area comprising the at least one analysis element, transparent to electromagnetic radiation, preferably with a wavelength of the electromagnetic radiation of at least 200 nm, more preferably in a range of the wavelength of the electromagnetic radiation of 200 nm to 1000 nm. This range includes in particular the range of ultraviolet radiation (approx. 200 nm to approx. 400 nm wavelength), the range of radiation visible to the human eye (approx. 400 nm to approx. 800 nm wavelength) and the infrared range (from approx. 800 nm wavelength).

The at least one flexible cover layer preferably has a modulus of elasticity - tensile strength - of 100 MPa to 4000 MPa, preferably 1500 MPa to 3000 MPa, each determined in accordance with DIN EN ISO 527-3: 2003-07 (“Plastics - Determination of

Tensile properties - Part 3: Test conditions for films and sheets - Date of issue: 2003-07), preferably at room temperature (25 ° C). The determination of the

The tensile modulus of elasticity takes place on film test strips by means of a tensile testing machine (for example a tensile testing machine from ZwickRoell GmbH & Co. KG, Ulm, DE). The width of the film strips is preferably 15 mm +/- 0.1 mm, the length of the film strips is preferably 100 mm +/- 0.5 mm or 50 mm +/- 0.5 mm for film materials with high elongation. The test speed for a film length of 100 mm is 10 mm / min +/- 1 mm / min or the

The test speed for a film length of 50 mm is 5 mm / min +/- 1 mm / min.

The at least one flexible cover layer preferably has structures that are stable on a microscopic scale and at the same time can represent a very thin layer on a macroscopic scale, which has a low wall thickness of the analysis element on a macroscopic scale and easy production of the

Allow structural elements via known methods, for example role-to-role replication.

For example, a thermoplastic film, for example PET film, can have a coating of a printed and / or poured and / or knife-coated and / or sprayed, preferably radiation-curing, lacquer as the carrier layer. On or in a surface of this lacquer layer, preferably the side of the lacquer layer facing away from the surface of the carrier layer, at least one structural element is arranged, which is further preferably a distance of approx have the next structural element. The distances in different directions can also be different. For example, the distances across the flow direction can be larger and smaller in the flow direction. The distances can also vary locally. For example, the distances in one direction can become increasingly linear or non-linear. The distances can also be in two at the same time

Directions vary accordingly or the distances can also form a pattern or motif. It is preferably sufficient if the minimum distance between two or more arranged structural elements corresponds to approximately two to four times the thickness of the, in particular, multilayer, flexible cover layer.

The structural elements can be introduced, in particular replicated, directly into the carrier material of the flexible cover layer. Their ordered position allows in particular the determination of partial volumes and facilitates the quick determination of the functional focal plane. In addition, you can Irregularities in the mapping of this ordered position of the structural elements can be used for error correction.

In a preferred embodiment, the at least one comprises flexible

Cover layer on a carrier layer, a cover layer composed of at least one replication lacquer, the structures of the at least one analysis element being arranged on a surface of at least one side of the cover layer.

The flexibility of the carrier layer and the cover layer can differ from one another or also be similar. For example, the carrier layer and also the cover layer can be composed of thermoplastic polymers which have similar mechanical properties, in particular similar e-modules. Alternatively, the carrier layer can be made up of thermoplastic polymers and the cover layer, on the other hand, can be made up of crosslinking and thermosetting, in particular radiation-curing, polymers, the carrier layer and the

Cover layer each have different mechanical properties, in particular different e-modules. In particular, the thermoplastic cover layer can have an e-modulus of, for example, 2000 MPa and the crosslinked cover layer can have an e-modulus of, for example, 9000 MPa. The cover layer can have a thickness of less than 30 μm, preferably less than 10 μm and particularly preferably less than 5 μm.

The structures of the at least one analysis element can be designed, for example, in the form of a positive structure or a negative structure. In particular, a positive structure can be formed by structures that are predominantly convex or raised relative to the surrounding surface, whereas a negative structure can in particular be formed by structures that are predominantly concave or sunk in relation to the surrounding surface.

More preferably, the at least one replication lacquer comprises at least one polymer, which is preferably selected from the group consisting of thermoplastics, thermosets,

thermoplastic elastomers (TPE), preferably made of PET, PMMA, ABS, PEN, BOPP, PVC, PA, particularly preferably made of PET or PEN and mixtures thereof Preferably, the at least one flexible top layer furthermore has at least one decorative element, the at least one decorative element influencing the surface texture and / or the color of the surface of the at least one flexible top layer, preferably the top layer, the at least one decorative element preferably being a motif, is designed as a decor, for example single image decor or endless decor, as a pattern, or a combination thereof.

More preferably, the at least one decorative element is designed at least in some areas as a decorative layer, which is preferably from the group consisting of transparent and / or colored lacquer layers, in particular comprising one or more

Dyes and / or pigments, replication layers with molded optically and / or functionally active surface structure, reflection layers, in particular opaque reflection layers, transparent reflection layers, metallic

Reflective layers or dielectric reflective layers, optically variable layers, optically active layers, interference multilayer systems,

Volume hologram layers, liquid crystal layers, in particular cholesteric liquid crystal layers, electrically conductive layers, antenna layers,

Electrode layers, magnetic layers, magnetic storage layers and

Combinations thereof is selected.

More preferably, the at least one flexible cover layer and / or the at least one decorative element has further replication layers, coatings, light coupling elements, coloring, register marks, lettering,

Position marks, reference marks, setting aids / focusing aids for microscopes, markings (numbers, barcodes), quality marks, microlenses and / or partial metal layers.

Register or register or register accuracy or register accuracy is preferably a positional accuracy of two or more elements and / or layers and / or plies, here in particular a donor foil and / or a foil element, for example a cover layer, to the recipient foil, for example

Base position to understand. The register accuracy should move within a specified tolerance and be as low as possible. At the same time, the register accuracy of several elements, sub-areas, in particular one or more

Foil elements, foils, plies and / or layers to one another are an important feature in order to increase process reliability.

The precise positioning takes place in particular by means of markings, in particular by means of sensor marks, preferably optically detectable registration marks or register marks. These markings, in particular registration marks or register marks, preferably represent either special separate elements or areas or layers or are preferably themselves part of the elements or areas or layers to be positioned.

The at least one flexible cover layer can be locally thickened, for example provided with reinforcing ribs or the like, or thinned. In addition, further decorative or functional layers or elements can be arranged on the structure side or on the side facing away from the structure. Such arrangements can lead to a rapid, directed development of the suction effect and thus the filling speed.

Further preferably, on the side of the cover layer, preferably cover layer, having the at least one channel, at least one adhesive layer is arranged, which preferably crosslinking at least thermoplastic components

Includes components or combinations thereof.

Typical thermoplastic adhesive components are, for example, polyethylene; Polyvinyl acetate and its copolymers; Acrylic resins and their copolymers;

Methacrylic resins and their copolymers, polyvinyl butyral, polyamides, polyesters, chloroprene resins, polypropylenes, polyvinyl alcohol, polycarbonates, polyurethanes.

Typical crosslinking adhesive components are, for example, melamine resins and phenolic resins; Polyurethane resins, UV crosslinking resins, cationic crosslinking resins, electron beam crosslinking resins. Thermoplastic components and cross-linking components can also be combined in one adhesive layer. It is also possible to arrange thermoplastic adhesive layers and crosslinking adhesive layers adjacent to one another in area-specific areas. It is also possible in several layers on top of each other

to arrange thermoplastic adhesive layers and crosslinking adhesive layer adjacent to one another.

Plasticizers and / or wetting agents can also be added to the adhesive layer.

The adhesive layer can be arranged as a flat adhesive layer or as a partial adhesive area on the cover layer.

By arranging the adhesive layer on the side of the cover layer, preferably the cover layer, having the at least one analysis element, the adhesion of the base layer to the cover layer is preferably improved. In addition, the adhesive layer can form side edges or side walls of the flow channel, at least in sections, as a partial adhesive area.

The at least one top layer, preferably top layer, can preferably have additional structures within which at least one adhesive can be applied or which are covered after the application of adhesive and application of the base layer to the top layer and are optically not perceptible or only to a reduced extent.

A microfluidic arrangement according to the invention comprises at least one, preferably rigid, base layer which more preferably has a thickness of at least 200 μm, preferably of at least 600 μm.

The at least one, preferably rigid, base layer is preferably constructed from at least one polymer, at least one glass, at least one metal, at least one semiconductor material or a combination thereof. The at least one, preferably rigid, base layer preferably has a

Modulus of elasticity greater than 1000 MPa, preferably greater than 2000 MPa, particularly preferably greater than 2500 MPa, each determined in accordance with DIN EN ISO 527-3 (date of issue: 2003-07), preferably determined at room temperature (25 ° C.).

The at least one, preferably rigid, base layer is at least partially transparent to electromagnetic radiation, preferably with a wavelength of the electromagnetic radiation of at least 200 nm. This range includes in particular the range of ultraviolet radiation (approx. 200 nm to approx. 400 nm wavelength) , the range of radiation visible to the human eye (approx. 400 nm to approx. 800 nm wavelength) and the infrared range (from approx. 800 nm wavelength). More preferably, at least one, preferably rigid, base layer is at least partially transparent to electromagnetic radiation, preferably with a wavelength of the electromagnetic radiation of at least 200 nm to 1000 nm.

In this way, for example, an optical evaluation of a liquid to be examined can take place in a microfluidic arrangement according to the invention, for example by irradiating electromagnetic radiation through the base layer.

The at least one, preferably rigid, base layer can furthermore comprise or consist of a CCD sensor or a CMOS sensor, for example.

As an alternative to the fact that the base layer comprises or consists of a CCD sensor or a CMOS sensor, it is possible that such a CCD sensor or CMOS sensor as a separate element, in particular as components of a

Measuring device or analysis device preferably immediately adjacent to the

Base layer is arranged. This separate sensor can be in direct contact with the base layer or there are still optically effective elements between the base layer and the sensor

Structures, for example microlenses or other micro-optical arrangements, are provided in order to optically adapt the sensor to the microfluidic arrangement and thus enable the components in the sample, for example cells, to be mapped on the sensor. The microlenses or other micro-optical arrangements can be part of the base layer or be provided as a separate layer. The at least one, preferably rigid, base layer further preferably has macroscopic structures with a minimum structure size of greater than 10 μm, preferably at least one or more of the following functional elements: inlet, outlet, opening, depression, bulge, wall element,

Channel element, antechamber, mixing chamber, collecting chamber, analysis chamber or combinations thereof. A collecting chamber is preferably arranged behind an analysis chamber in the flow direction.

The functional elements can be “empty”, partially filled or completely filled. For example, a collecting chamber can be filled to 50% with an absorbent agent in order to prevent liquids that get into the collecting chamber from running out in an uncontrolled manner. Examples of fillings are

Cellulose fibers that soak up liquids, activated carbon to absorb liquids and / or solids, etc.

It is also possible that an inlet or outlet chamber with

Filtration elements is equipped, so that in the case of the inlet chamber certain proportions of the liquid to be examined are separated.

The at least one, preferably rigid, base layer can furthermore have at least one decorative element, the at least one decorative element being the

Surface texture and / or the color of the surface which influences the at least one, preferably rigid, base layer, the at least one

Decorative element is preferably designed as a motif, as a decoration, for example single image decoration or endless decoration, as a pattern, or a combination thereof.

The at least one decorative element is preferably designed at least in some areas as a decorative layer, which is preferably from the group consisting of transparent and / or colored lacquer layers, in particular comprising one or more

Dyes and / or pigments, replication layers with molded optically active surface structure, reflection layers, in particular opaque

Reflective layers, transparent reflective layers, metallic

Reflective layers or dielectric reflective layers, optically variable Layers, optically active layers, multilayer interference systems, volume hologram layers, liquid crystal layers, in particular cholesteric liquid crystal layers, electrically conductive layers, antenna layers,

Electrode layers, magnetic layers, magnetic storage layers and

Combinations thereof is selected.

More preferably, the at least one, preferably rigid, base layer has further coatings, light coupling elements, colors, register marks,

Labels, position marks, setting aids / focusing aids for microscopes, identifications (numbers, barcodes), quality marks, labeling fields, logos and / or partial metal layers.

In a preferred embodiment, the at least one cover layer is provided in the form of a transfer film, the transfer film furthermore having at least one carrier layer which is placed on the at least one analysis element

opposite side of the at least one cover layer is detachably arranged.

The at least one carrier layer preferably comprises at least one

Carrier layer made of a polyester, a polyolefin or a combination thereof, in particular made of PET, which preferably has a layer thickness between 4 μm and 150 μm, preferably between 10 μm and 50 μm.

Preferably, the at least one carrier layer further comprises at least one release layer which is arranged on the side of the carrier layer facing the cover layer.

The at least one release layer preferably comprises at least one wax, preferably montan ester wax, at least one silicone, at least one

Polyurethane or acrylate or a combination thereof, preferably in a layer thickness of 0.1 nm to 100 nm.

Alternatively, the at least one cover layer can be in the form of a laminating film

are provided, wherein the laminating film furthermore has at least one carrier layer which is arranged, preferably non-detachably, on the side of the at least one cover layer opposite the at least one channel.

The laminating film preferably further comprises at least one adhesive layer, which is arranged on the side of the carrier layer facing the cover layer. The

The carrier film can be peeled off after the top layer has been applied.

A protective layer is preferably also detachably arranged on the side of the cover layer containing the at least one analysis element, which is preferably removed from the cover layer before the at least one cover layer is arranged on the base layer.

It is further preferred in step c) the at least one, preferably rigid,

Base layer arranged inextricably on the top layer.

The at least one cover layer used in the method according to the invention can be provided, for example, in the form of at least one transfer film which has at least one transfer layer detachably arranged on a carrier layer. On the at least one cover layer, in particular the surface of the at least one cover layer having the at least one structural element is arranged on the side of the at least one transfer layer opposite the carrier layer.

A transfer film used in the method according to the invention is used for

Transfer of at least one transfer layer to the at least one base layer used, the side of the at least one transfer layer opposite the carrier layer being at least partially arranged, preferably non-detachably, on at least one surface of at least one side of the base layer.

With the transfer layer, the at least one cover layer and the at least one analysis element are transferred to the at least one base layer.

In particular, the at least one structural element that is at least on one surface of the side opposite the carrier layer of the at least a transfer layer is arranged on the at least one surface of the at least one side of the base layer, preferably non-detachably, while maintaining at least one, at least partially completely covered

Arranged flow channel.

After the transfer layer has been arranged on at least partial areas of the at least one surface of at least one side of the base layer, the

Carrier layer removed from the transfer layer, preferably completely, so that only the transfer layer on at least partial areas of at least one surface of at least one side of the base layer while maintaining a

microfluidic arrangement according to the invention remains.

It can be provided that the at least one carrier layer comprises at least one carrier layer, preferably carrier film, made of a polyester, a polyolefin or a combination thereof, in particular PET, which preferably has a layer thickness between 4 μm and 100 μm, preferably between 10 μm and 50 gm.

It can be provided that the at least one carrier layer further comprises at least one release layer, which is arranged on the side of the carrier layer facing the cover layer. The at least one release layer preferably comprises at least one wax, preferably montan ester wax, at least one silicone, at least one polyurethane, at least one acrylate or a combination thereof, preferably in a layer thickness of 0.1 nm to 100 nm.

The release layer preferably remains on the carrier layer, preferably carrier film, after the release.

It can be provided that the transfer film has a second carrier layer, preferably carrier film, on its transfer layer, in particular that side of the transfer layer facing the surface of the cover layer which has at least one structural element. The second carrier layer, preferably carrier film, can be designed as a protective layer for the surface of the cover layer having the at least one structural element.

The second transfer film can preferably have a master relief structure on its side facing the transfer layer, the surface of the cover layer having the at least one structural element preferably having a relief structure complementary to the master relief structure of the second carrier film.

The master relief structure is preferably introduced into the second carrier layer, preferably carrier film, and / or onto the second carrier layer, preferably

Carrier film, applied, preferably by method steps and devices that have proven themselves in practice and are suitable for mass production, for example by a roll-to-roll process.

The master relief structure can preferably be formed by an embossing in the second carrier layer, preferably carrier film. Embossing processes can be provided which are used in the production of film bodies. If the second carrier layer, preferably carrier film, is a thermoplastic carrier layer, preferably carrier film, the master relief structure can be introduced with a thermal embossing process using an embossing roller under pressure and temperature. A second carrier layer, preferably carrier film, embossed in this way is sufficiently stable to prevent the deformation of the

Exclude structure layer when hot embossing the second relief structure.

However, it can also be provided that the second carrier layer, preferably carrier film, has a layer in which the master relief structure is molded. It can be provided, for example, to apply a thermoplastic replication lacquer layer to the second carrier layer, preferably carrier film, which

To dry the lacquer layer and then to mold the master relief structure in this lacquer layer.

It can further be provided that a UV-curable replication lacquer is applied to the second carrier layer, preferably carrier film, and during the application to introduce the master relief structure with an embossing roller. The UV source required for curing the UV lacquer can either be arranged in the transparent embossing roller or under the second carrier layer, preferably carrier film. In a modified embodiment, it can be provided that the master relief structure is molded by partial irradiation of the UV-curable replication lacquer layer of the second carrier layer, preferably carrier film, and the non-cured areas

then removed by washing.

To form the at least one structural element, it can be provided that the at least one flexible cover layer is preferably placed on the second carrier layer

Carrier film, in the form of a replication lacquer, for example a thermoplastic replication lacquer and / or UV-curable replication lacquer, to be applied and the at least one structural element to be molded, preferably using at least one embossing roller.

The use of a UV-curable replication lacquer is advantageous because the UV-curable lacquer can be made particularly flowable and thus very small

Able to fill cavities of the master relief structure completely.

The advantage is that UV-curable lacquer forms a particularly temperature-stable layer. It can therefore also be provided that at least one

To form structural element from two layers, wherein advantageously the first layer can be formed from UV-curable lacquer and the second layer from thermoplastic lacquer. Both layers should advantageously be designed with the same optical refractive index, so that the layer structure is optically imperceptible.

In a further advantageous embodiment it can be provided that the second carrier layer, preferably carrier film, has partial printing. The partial printing can be particularly advantageous in order to form master relief structures with a small depth-to-width ratio in a particularly simple manner.

The thickness of the printed layer can be set differently, for example between 2 μm and 5 μm. The partial printing can also be provided in addition to the above-described embossing of the master relief structure, for example to individualize the master relief structure.

The second carrier layer preferably comprises at least one carrier layer, preferably carrier film, made of a polyester, a polyolefin or a

Combination thereof, in particular of PET, which preferably includes a

Layer thickness between 4 pm and 150 pm, preferably between 10 pm and 50 pm.

It can be provided that the second carrier layer further comprises at least one release layer which is arranged on the side of the second carrier layer facing the cover layer. The at least one release layer preferably comprises at least one wax, preferably montan ester wax, at least one silicone, at least one polyurethane, at least one acrylate or a combination thereof, preferably in a layer thickness of 0.1 nm to 100 nm.

In a preferred embodiment, one in the inventive

Method used transfer film on one or more separate, juxtaposed transfer layers, each comprising a separate, juxtaposed cover layer or cover layer areas, wherein in each case a cover layer, in particular the surface of the cover layer having the at least one structural element, on the, the first carrier layer

opposite side of each transfer layer is arranged.

The transfer film is preferably provided as a continuous, multi-layer base film, preferably severing along at least one boundary line that defines at least one first sub-area and separates the at least one first sub-area from a second sub-area.

The transfer film further preferably comprises a second carrier layer, which is arranged on the side of the first carrier layer opposite the transfer layer.

The transfer film further preferably has a second carrier layer and one applied to the surface of the first carrier layer facing away from the transfer layer first layer of adhesive, with the first layer of adhesive between the first

Carrier layer and the second carrier layer is arranged and the first adhesive layer is activated in a first region that at least partially covers at least one first partial region of the base film, so that the base film is in the

at least one first sub-area adheres to the second carrier film and is not activated, not provided, only partially provided or deactivated in a second part adjoining the at least one first sub-area, and the first carrier film along the at least one first sub-area defining and the at least a first sub-area is severed by border lines separating a second sub-area of the base film and a part of the base film comprising the second sub-area is peeled off from the second carrier film. This configuration is particularly advantageous because both optical and other defects in the first and / or second carrier film (e.g.

Background fluorescence) does not affect the functionality of the microfluidic

Arrangement.

The base film preferably has a release layer arranged between the first carrier layer and the transfer layer. It is also possible that the material or the surface properties of the first carrier layer,

preferably carrier film, and the layer of the transfer layer facing the first carrier layer, preferably carrier film, are selected such that the

Transfer layer is detachable from the first carrier layer, preferably carrier film.

It is further preferred that no release layer is contained between the first carrier layer, preferably carrier film, and the transfer layer. According to this

Embodiment is the first adhesive layer and one between the

Transfer layer and the target substrate arranged second adhesive layer is chosen so that the adhesive force caused by the activated first adhesive layer between the first carrier layer, preferably carrier film, and the second carrier layer, preferably carrier film, is less than that caused by the activated second adhesive layer between the transfer layer and the target substrate Adhesive strength is. This makes it possible, after activating the second adhesive layer, to peel off the second carrier layer, preferably carrier film, from the first sub-area of the base sheet and thus the entire first sub-area of the base sheet, ie Transfer layer and first carrier layer, preferably carrier layer, to be applied to the target substrate by means of a transfer process.

It has proven useful that the first adhesive layer is applied to the first carrier layer, preferably carrier film, and then the second carrier layer, preferably carrier film, is applied to the first adhesive layer. However, it is also possible that the first adhesive layer is applied to the second carrier layer, preferably carrier film, and then the film body comprising the second carrier layer, preferably carrier film, and the first adhesive layer is applied to the first carrier layer, preferably carrier film, and thus the first

Adhesive layer is applied to the first carrier layer, preferably carrier film, with the aid of the second carrier layer, preferably carrier film.

The first adhesive layer used is preferably an adhesive layer that can be activated by electromagnetic radiation, in particular an adhesive layer consisting of a UV-activatable adhesive that can be activated by irradiation with UV light. In this way, on the one hand, the advantage is achieved that the activation of the first adhesive layer in the first area can be precisely controlled. Furthermore, it has been shown that when such an adhesive layer is used, detachment of the first carrier layer, preferably carrier film, from the second carrier layer, preferably carrier film, can be reliably prevented during a subsequent transfer process and the transfer result can also be further improved in this way.

The first adhesive layer is preferably applied over the full area both in at least one first partial area and in the second partial area on the surface of the carrier layer, preferably carrier film, facing away from the transfer layer. The activation of the first adhesive layer in the first area then takes place in the following before the second part of the base film is peeled off. The first adhesive layer can be applied to the first carrier layer, preferably carrier film, for example by means of a printing process, for example gravure printing or screen printing, but also by means of pouring, spraying or knife-coating. The first adhesive layer is preferably activated by irradiation in the first area after application of the second carrier layer, preferably carrier film, so that the second carrier layer, preferably carrier film, adheres to the first carrier layer, preferably carrier film, in the first region. The material of the first adhesive layer is here in relation to the first carrier layer, preferably carrier film, and the second carrier layer, preferably carrier film, more preferably selected so that the adhesion between the first carrier layer, preferably carrier film, and the second

Carrier layer, preferably carrier film, after activation of the first adhesive layer, even at room temperature (20 ° C.), higher than the adhesion mediated by the release layer between the transfer layer and the first carrier layer, preferably

Carrier film is. Furthermore, the material of the first adhesive layer with respect to the first carrier layer, preferably carrier film, and the second carrier layer, preferably carrier film, is preferably chosen so that the adhesion between the first

Carrier layer, preferably carrier film, and the second carrier layer, preferably carrier film, when the first adhesive layer is not activated, less than the adhesion between the first carrier layer mediated by the release layer, preferably

Carrier film and transfer layer both at room temperature (20 ° C) and at embossing temperature (180 ° C).

Furthermore, it has proven advantageous that the adhesion properties between the first adhesive layer and the first and / or second carrier layer, preferably carrier film, are achieved by applying primers, adhesion promoters or by corona, flame or plasma treatment of the first or second carrier layer, preferably Carrier film.

According to a preferred embodiment of the invention, the first

Adhesive layer is irradiated by a radiation source arranged at a distance in the direction of the side of the second carrier layer, preferably carrier film, facing away from the transfer layer. The radiation source is preferably arranged at a distance of more than 10 mm from the second carrier layer, preferably carrier film. The radiation source used is preferably a UV radiation source which exposes the first adhesive layer to collimated light, preferably UV light. For example, UV lamps with a downstream collimator or a laser are suitable as the radiation source. By exposing the first adhesive layer in this way, it is possible to

Exposure of the first adhesive layer regardless of the configuration of the

To choose the transfer position of the base film. The second carrier layer, preferably carrier film, preferably consists of a material which is suitable for the wavelength range of the radiation source used for the exposure

is largely transparent.

A selective exposure of the first adhesive layer in the desired areas, for example the selective irradiation of the first adhesive layer in the first area to activate the first adhesive layer in the first area, can be achieved by appropriate control of the radiation source or by arranging an exposure mask in the beam path between the radiation source and the first adhesive layer.

It is also possible to deactivate the first adhesive layer by exposure in the second area. For example, it is possible to use a corresponding adhesive for the first adhesive layer which can be deactivated, for example, by means of UV radiation. Furthermore, it is also possible to use a UV-activatable adhesive for the first adhesive layer, which cures when irradiated with UV light and to irradiate the first adhesive layer in the second area before applying the second carrier layer, preferably carrier film. The first adhesive layer is thus cured in the second area before the second carrier layer, preferably the carrier film, is applied, so that after the second carrier layer has been applied, preferably

Carrier film, adhesion of the second carrier layer, preferably carrier film, is no longer possible in the second area, since the first adhesive layer has already cured and thus deactivated in this area.

A laser is preferably used as the radiation source which is controlled in such a way that the first adhesive layer is irradiated in the first area but not in the second area and / or is irradiated in the second but not in the first area.

This can be achieved, for example, by appropriate control of an actuator which determines the position of the laser or the deflection angle of the laser beam. More preferably, an exposure mask is arranged in the beam path between the radiation source and the first adhesive layer, which is shaped and arranged such that the first adhesive layer is irradiated in the first area, but not in the second area, or the first adhesive layer in the second area, but not in the first area is irradiated. The exposure mask can be part of a drum or belt exposure unit.

The transfer layer is preferably used to control the irradiation of the first adhesive layer.

For this purpose, the first adhesive layer is preferably applied from a side facing away from the first carrier layer, preferably carrier film

The radiation source arranged at a distance from the transfer layer and arranged at a distance is irradiated. The transfer situation is thus in

Beam path arranged between the radiation source and the first adhesive layer.

The transfer layer preferably has an opaque one which is provided in the first or second area and not in the second or first area

provided layer, which acts as a masking layer for controlling the

Irradiation of the first adhesive layer is used. For example, it is possible to use a metallic reflective layer as the transfer layer

To use masking layer to control the irradiation of the first adhesive layer. This makes it possible to control the exposure of the first adhesive layer in register with the design of the decorative layer.

The metallic reflective layer is preferably a metal layer made of chromium, copper, silver or gold or an alloy of such metals, which can be vapor-deposited in a vacuum in a layer thickness of 0.01 μm to 0.04 μm, for example.

In a first irradiation step, the first adhesive layer is preferably applied from one in the direction of that from the first before the second carrier film is applied

Carrier film facing away from the transfer layer and arranged from the Transmission layer spaced apart radiation source through the as

Masking layer acting layer irradiated and deactivated in the second area. In a second irradiation step, after the application of the second carrier layer, preferably carrier film, the first adhesive layer is then arranged from a side of the second carrier layer, preferably carrier film, facing away from the first carrier layer, preferably carrier film, and from the second carrier layer, preferably carrier film, spaced apart radiation source irradiated and activated in the first area.

The exposure of the first adhesive layer can - as described above - take place in one step. However, it is also possible for the exposure to take place in several stages. It is thus possible, for example, that the adhesive layer is activated in a first exposure step, but the adhesive does not yet fully cure. After the second part of the base film has been peeled off, the remaining film with the second carrier layer, preferably carrier film, and the first part of the base film is then irradiated, the first adhesive layer hardening completely.

The transfer layer can preferably have marks which are used to determine the first and second areas of the first adhesive layer and / or for

Determination of the first and second partial areas of the base film can be used. These marks thus represent register marks. The marks can be formed from a printing material, from a surface relief, from a magnetic or an electrically conductive material. For example, the marks can be optically readable register marks which differ from the background in terms of their color value, their opacity or their reflective properties. The marks can also be a macroscopic or diffractive relief structure that deflects the incident light in a predetermined angular range and differs from the

Visually distinguish the background area. However, the register marks can also be register marks which can be detected by means of a magnetic sensor or a sensor which detects the electrical conductivity. The marks are detected, for example by means of an optical sensor and by means of the marks the severing of the carrier layer, preferably the carrier layer, the activation of the first adhesive layer, the deactivation of the first adhesive layer and / or the Controlled application of the first adhesive layer. Thus, the transfer layer has, for example, optically readable register marks which indicate the irradiation of the first adhesive layer and preferably also the severing of the first

Carrier layer along the boundary line between the at least one first

Sub-area and the second sub-area controls. This, too, is a

in-register activation of both the first adhesive layer and one

Accurate separation of the carrier layer, preferably carrier film, possible for the design of the transfer layer.

The marks are preferably arranged in the second partial area of the base film. The marks can be formed here, for example, as lines or stripes, which preferably run transversely to the longitudinal direction of the film web that forms the base film. The marks are preferably arranged between two first areas of the base film.

Furthermore, each first part of the base film is preferably one or more

Allocated register marks.

Furthermore, it is also possible for the first adhesive layer to be formed by a hot-melt adhesive layer or by an adhesive layer that can be activated by pressure.

Furthermore, it is also possible for the first adhesive layer to be formed by a latently reactive adhesive layer, preferably by a latently reactive hot-melt adhesive layer. A latently reactive adhesive layer is an adhesive layer that has not yet fully hardened after activation and whose complete hardening and thus development of the full adhesive force only after one

predefined time from activation is reached under predefined environmental conditions. For example, if it is a latently reactive one

Hot-melt adhesive layer or around a latently reactive cold-melt adhesive layer, the adhesive layer is activated in a first step by temperature and / or pressure and achieves between 10% and 90% of the maximum adhesive force. After a predetermined time dependent on the adhesive composition, for example 10 minutes to 72 hours, the adhesive layer then cures completely and develops its full adhesive strength. For example, after removing the second part of the Base film, the remaining film with the second carrier layer, preferably

Carrier film, and the first part of the base film stored for a predefined time at room temperature and optionally at an elevated temperature to cure the latent reactive adhesive layer, thus achieving complete curing of the latent reactive adhesive layer. In this context, activation of the first adhesive layer is understood to mean, in particular, an action on the adhesive layer which causes the adhesive layer to trigger a chemical reaction which leads to an at least 10% increase in the adhesive force after the chemical reaction has largely ended.

A microencapsulated reactive adhesive can also be used as the latently reactive adhesive, as is e.g. is available under the name Purbond HCMO from Ebnöther AG, Sempach, Switzerland. Such an adhesive can

for example in a powder coating process at temperatures between about 60 ° C. to 70 ° C. on the first or second carrier layer, preferably carrier film, the fixing taking place at this temperature forming a lacquer-like adhesive layer which is not yet activated. The microcapsules are broken open and the adhesive hardens in this area by exerting a streak and / or pressure.

According to a preferred embodiment of the invention, the first adhesive layer consists of a hard-working adhesive and the first adhesive layer is applied by means of a heated embossing stamp in the first, but not in the second area before the

Peeling off the second part of the base film is activated.

Furthermore, it is also advantageous if the first adhesive layer is deactivated in the second area by means of overprinting with a deactivation layer or the first

Adhesive layer is printed onto the first and / or second carrier layer, preferably carrier film, in the first area, but not in the second area. Furthermore, it is also possible for the first adhesive layer to be applied in the first area and in the second area with different surface densities, so that the average adhesive force per unit area, in particular per cm ^2, in the first and second area

differs. It is also advantageous if the first adhesive layer in the second area is deactivated by means of overprinting with a deactivation layer or if the first adhesive layer is printed onto the first and / or second carrier film in the first area, but not in the second area. The deactivation layer can be made, for example, of silicone or silicone-containing substances or of polytetrafluoroethylene (PTFE, ^Teflon® ).

In this embodiment, the first adhesive layer is preferably printed in a dot-like pattern in the first and / or second surface area, the difference in surface density being able to be achieved by varying the dot sizes and / or the grid widths between the adhesive dots. Furthermore, it is also possible to apply the adhesive layer over the entire surface in the first area and to apply the adhesive layer only in the form of a punctiform grid in the second area or not to apply the first adhesive layer in the second area and to apply the adhesive layer in a punctiform grid in the first area. The mean surface coverage of the first and / or second carrier layer, preferably carrier film, with the first adhesive layer differs in the first area from that in the second area by at least 15%.

The second carrier layer, preferably carrier film, is preferably laminated onto the base film by means of two opposing rollers.

According to a preferred embodiment of the invention, the

Transfer layer, the release layer and the first carrier layer, preferably

Carrier film, completely severed along the borderline defining the at least one first partial area. It is also possible here that the second carrier layer, preferably carrier film, is also partially cut through. In this case, however, it is preferable to ensure that the second carrier layer, preferably carrier film, is severed less than 50%, preferably less than 90%.

The first carrier layer, preferably carrier film, is preferably severed by means of punching, for example by means of a rotary punch or by means of a laser. The first carrier layer is preferably severed, preferably

Carrier film, in register with the boundary line between the first and second area. On the other hand, the method according to the invention does not require high

Register accuracy between the process structuring the first adhesive layer (exposure, printing, embossing) and the severing process (punching), so that cost-effective, large-scale industrial processes can be used.

It is also advantageous that the film body formed by the base film, the second carrier layer, preferably carrier film, and the first adhesive layer is processed by means of a hot stamping stamp which simultaneously activates the first adhesive layer in the first sub-area and the first carrier layer, preferably the carrier film, along the at least partially punched through at least one boundary line defining a first partial area. This achieves a very high register accuracy between these two processes and also the number of

Processing steps reduced.

Preferably, after peeling off the second part of the base film, the remaining film with the second carrier layer, preferably carrier film, and the first part of the base film is used as a transfer film, in particular hot stamping film, for producing the microfluidic arrangement according to the invention.

It is also possible for this transfer film to have a multiplicity of first partial areas, each of which includes at least one analysis element that is used in each case by means of transfer to a base layer.

For example, one or more analysis elements, which are in fluid connection with one another after the transfer, for example, can be transferred to a base layer.

For this purpose, after peeling off the second part of the base film, the remaining film with the second carrier layer, preferably carrier film, and the first part of the base film can be placed on a target substrate, one or more first partial areas of the base film can be placed on the target substrate by activating one between the Decorative layer and the target substrate arranged adhesive layer applied and the multilayer body comprising the first carrier layer, preferably carrier film, the first adhesive layer and the second carrier layer, preferably carrier film, from the transfer layer of the applied one or more first partial areas of the

Base film can be peeled off.

For this purpose, a second adhesive layer, which is preferably a hot-melt adhesive layer, is applied to the side of the transfer layer facing away from the first carrier layer, preferably carrier film. Furthermore, it is also possible for the second adhesive layer to be a cold adhesive layer or a latently reactive hot melt adhesive layer.

Different adhesives are preferably used for the first adhesive layer and for the second adhesive layer. For example, it is possible to use a cold adhesive for the first adhesive layer and a hot melt adhesive for the second adhesive layer. If hot-melt adhesive layers are used as the first and second adhesive layers, it is advantageous to choose hot-melt adhesive layers which

have different activation temperatures, the

Activation temperature of the first adhesive layer higher than that of the second

Adhesive layer is. This improves the transfer result.

A transparent plastic film with a thickness of more than 6 μm, preferably a thickness between 6 μm and 250 μm, is preferably used as the second carrier film. However, it is also possible to use a paper substrate or Teslin® (matt, white, uncoated, single-layer polyethylene film) as the second carrier film. A plastic film with a thickness between 4 μm and 75 μm is preferably used as the first carrier film.

According to a preferred exemplary embodiment of the invention, two or more first partial areas are provided and each of the first partial areas is enclosed by the second partial area formed as a coherent area.

This makes it easier to pull off the second area of the base film. The first area preferably covers at least 50% of each first sub-area, more preferably more than 70% of each first sub-area. It is furthermore also possible for the first area to completely cover each first partial area. Furthermore, the second sub-area preferably covers the first area by less than 5%. This measure further ensures that the second part of the base film can be pulled off with high reliability.

In the method according to the invention, the base film described above can be designed both as a transfer film and as a laminating film. If the base film is designed as a transfer film, then in particular the transfer layer is the

Base film is transferred to a substrate and then the first carrier layer, preferably carrier film, is peeled off therefrom and preferably remains on the second carrier layer, preferably carrier film. One is particularly preferred here

Release layer arranged between the transfer layer and the first carrier layer, preferably carrier film.

If the base film is designed as a laminating film, then in particular the transfer layer and the first carrier layer, preferably carrier film, of the base film are transferred to a substrate and then the second carrier layer,

preferably carrier film, peeled off therefrom. Here, a release system is particularly preferably arranged between the first and the second carrier layer, preferably carrier film.

In addition, different shapes of the transfer film can be transferred with a constant stamp shape. It is also possible to transfer several, adjacent, isolated patches using a single stamp. The external shape of the patch does not have to match the external shape of the hot stamping stamp

to match. The hot stamping die is preferably selected to be larger than the part of the base film to be transferred.

In addition to a hot stamping stamp, with which hot stamping is carried out by means of stamping pressure and heat, an ultrasonic stamping stamp with a correspondingly designed counter pressure bearing can also be used, with which hot stamping is carried out using stamping pressure and ultrasound as an alternative form of energy. Likewise It is possible to use a roll laminator, in particular a semi-rotary laminator and / or multiple roll laminator (for example, several lamination rolls are arranged in series one behind the other for bank note applications). It is also possible to use the first carrier layer, preferably

Carrier film, with the help of a deflection roller, close to the second carrier layer printed with UV adhesive, preferably carrier film, without both

Carrier layers, preferably carrier films, to be pressed together. Additional, subsequent guide rollers then ensure the necessary contact between the two

Carrier layers, preferably carrier films, before curing with UV light.

It is also possible that the second partial area is not contiguous or also has sub-areas in which the entire film composite is removed. For example, in one embodiment each patch can have at least one enclosed free space, for example an inlet and / or outlet. The inlet and / or outlet can, for example, also during the

Punching process are generated. The inlet and / or outlet and / or also other openings or recesses can, for example, also be produced in a separate operation, for example in a separate punching process and / or in a separate laser process and / or in a separate milling pass.

The punching sheet used has, for example, two punching heights; one to only cover the transfer situation for the exemption of the first areas and, if necessary,

to cut through the existing brand area to be retained and another, higher area to cut through the entire film composite and thus create a hole. Also lasers with different settings for kiss-cut and

Punching through is possible in principle. The resulting film fragments are usually pressed or blown out of the film composite. The entire film composite is removed in this sub-area.

The second carrier layer, preferably carrier film, can be single-layer or multi-layer. The layers can consist of different or the same materials, for example paper and / or fabric and / or Teslin® and / or the same or different plastic layers. You can with each other be glued or, for example, by coextrusion or by

Multiple coatings can be made.

Different adhesives, in particular adhesives that can be activated differently, are therefore preferably used for the first and second adhesive layers. In particular, it is advantageous to use a radiation-activatable adhesive for the first adhesive layer and a thermally activated adhesive for the second adhesive layer. A thermally activated adhesive can be both reactive and non-reactive. Multi-layer structures are also possible. In addition to adhesives that can be activated by radiation, other reactive types of adhesives, such as one- and two-component systems (epoxy systems and / or, for example, with isocyanates as initiators for polymerization or crosslinking), are also possible.

It is advantageous here if the second adhesive layer is activated when the first part of the base film is hot-stamped onto a substrate. Before the hot stamping, the second adhesive layer therefore preferably has no tack. During hot stamping and activation, the interlayer adhesion between the carrier layers then increases, preferably by more than 50%, preferably more than 100%, particularly preferably more than 200%.

It is preferred if the hot stamping is carried out at a temperature of 80 ° C to 300 ° C, preferably from 100 ° C to 240 ° C, particularly preferably from 100 ° C to 180 ° C and / or with an embossing pressure of 10 N / cm ² to 10,000 N / cm ² , preferably from 100 N / cm ² to 5000 N / cm2 and / or with an embossing time of 0.01 s to 2 s, preferably from 0.01 s to 1 s.

It is also advantageous if the second adhesive layer is dried before the second carrier layer, preferably carrier film, is applied to the base film. This ensures that the second adhesive layer does not have any tackiness before the hot stamping. Varying surface coverage of the second adhesive layer (for example different in the first partial area) can also be used

Surface coverings indoors or outdoors) can be used. It is also advantageous if the second adhesive layer in a grid, in particular a Line grid or point grid with a grid density of 40 lines per cm to 80 lines per cm is applied.

It is particularly preferred if the second adhesive layer consists of one

thermoplastic adhesive with a glass transition temperature of 50 ° C to 150 ° C, preferably 100 ° C to 120 ° C is formed. The second adhesive layer can have a multilayer structure.

It is useful if the second adhesive layer is applied with a weight per unit area of 0.1 g / m ² to 10 g / m ² , preferably of 2 g / m ² to 5 g / m ² .

It is also advantageous if the first adhesive layer in a grid,

in particular a line grid or point grid with a grid density of 40 lines per cm to 80 lines per cm is applied. It is also possible to use varying surface assignments of the first adhesive layer (for example different surface assignments in the interior or exterior area in the first partial area).

It is useful here if the first adhesive layer is applied in the area of the printed grid with a layer thickness of 0.01 μm to 10 μm, preferably 2 μm to 5 μm.

The only partial application of the first adhesive layer ensures that the second adhesive layer has direct contact with both transfer layers and can thus increase the adhesion in the desired way.

The release system preferably consists of a waxy material which softens in particular due to the heat occurring during a hot stamping process. The total thickness of the release system is preferably between 0.01 μm and 4 μm. is softened and enables a reliable separation of the second carrier film.

The release system can be constructed in several layers. It comprises, for example, a layer of wax and a layer of a lacquer. As paints can

Acrylates, polyurethanes or cellulose derivatives are used. Prefers the lacquer layer has a thickness in the range from 0.1 μm to 3 μm, preferably in the range from 0.2 μm to 1.5 μm.

The layers of the release system on the multilayer body or on the

After application to the target substrate, security elements preferably have essentially the same area size as the security element or as the first partial areas. This is made possible in particular by the fact that the

Application, the release system is only activated within the first sub-area and is not activated in the adjacent second sub-area and therefore the release layer system remains on the second carrier film in the second sub-area. Due to the small thickness of the release system, the release layer system can be separated with sharp edges at the outer edges of the first partial area.

One or more layers of the release system preferably remain on the security element after application to the target substrate. This is preferably the case when the release system between the second carrier film and the

Adhesive layers is arranged. This makes it possible with the help of this

Layers to equip the outer surface of the multilayer body or security element with additional functions. Examples are better wettability or overprintability with further functional layers or, on the contrary, a hydrophobic function or other liquid-repellent functions or also the generation of an optical matt finish and / or an optical gloss and / or the generation of special tactile properties. It is also possible to add additional security prints in the visible wavelength range, UV range, IR range. Individual or all layers of the release layer system can be provided over the entire surface or only in partial surface areas.

It is also possible that, before the release system is applied, one or more auxiliary layers are applied to the side of the first carrier layer, preferably carrier film, of the base film facing away from the transfer layer. The auxiliary layers are then preferably between the first carrier layer

Carrier film, and arranged the release system. Examples are better wettability or overprintability with further functional layers or, on the contrary, a hydrophobic function or other liquid-repellent functions or the generation of an optical matting and / or an optical gloss and / or the generation of special tactile properties.

Individual or all layers of the release layer system can be provided over the entire surface or only in partial surface areas.

Preferably, the one or more layers of the release system are released from the transfer layer after application to the base substrate and the

Filler layers form the outer, free surface of the top layer.

The second carrier layer, preferably carrier film, is preferably laminated onto the base film by means of two opposite rollers.

In a preferred embodiment, a microfluidic arrangement of the present invention is designed as a cuvette.

A microfluidic arrangement according to one of claims 34 to 63 or a measuring system according to one of claims 65 or 66 can be used in particular in the in vitro examination of human or animal body fluids, in particular in the in vitro blood analysis.

In the following, the invention is explained by way of example on the basis of several exemplary embodiments with the aid of the accompanying drawings.

1 shows a schematic top view of a microfluidic arrangement.

2 shows a schematic sectional illustration of an embodiment of a microfluidic arrangement.

3 shows a schematic sectional illustration of a further embodiment of a microfluidic arrangement.

4a shows a schematic sectional illustration of a further embodiment of a microfluidic arrangement. 4b shows a schematic sectional illustration of a further embodiment of a microfluidic arrangement in the filled state.

FIGS. 5a and 5b each show a schematic sectional illustration of a further embodiment of a transfer film.

FIGS. 6a to 6c show schematic sectional illustrations to illustrate the method steps of the method according to the invention.

In the figures, elements that are the same or have the same function are the same

Reference numbers have been provided, unless otherwise stated.

1 shows a schematic top view of a microfluidic arrangement 1 comprising a, preferably rigid, base layer 2 and a flexible cover layer 9 arranged thereon. The cover layer 9 comprises an at least partially covered flow channel 4 and a first adhesive layer 11, which is located between the base layer 2 and the Cover layer 9, preferably on the edge of the cover layer 9, is arranged and

Base layer 2 and top layer 9 spaced apart. The flow channel 4 arranged in the microfluidic arrangement 1 is in fluid connection with inlet 41 and outlet 42, inlet 41 and outlet 42 each being at least round or oval

Through hole of cover layer 9 can be formed. The flow channel 4 also has a plurality of structural elements 13v designed as elevations.

2 shows a cross-sectional view of a preferred embodiment of the microfluidic arrangement 1. The section runs, for example, along a line AA in FIG. 1. The microfluidic arrangement comprises a, preferably rigid, base layer 2, which is constructed from a base layer 3, and one thereon arranged flexible cover layer 9. The cover layer 9 comprises a cover layer 10 and a first adhesive layer 11, which on the, the base layer 2 facing surface of the

Cover layer 10 is arranged and cover layer 10 and base layer 2, preferably base layer 3, are spaced apart. The cover layer 10 has a structural element 13v in the form of a depression, which is located on a surface of the base layer 2

facing side of the cover layer 10 is arranged. After arranging the side of the cover layer 9, preferably cover layer 10, having the structural element 13v on the base layer 2, preferably the base layer 3, the structural element 13v essentially forms the flow channel 4. The flow channel 4 also has in FIG The embodiment shown has several structural elements 13e in the form of convex elevations. The structural element 13e is arranged on a surface of the side of the flow channel 4 opposite the base layer 2, so that preferably between the side of the base layer 2, preferably the base layer 3 facing the cover layer 9, and the at least one structural element 13e in the diagram shown in FIG. 2, a distance is formed in an unfilled state of the microfluidic arrangement. Of course, designs are also conceivable in which the distance shown does not exist in the unfilled state. In a filled state of the microfluidic arrangement, shown for example in FIG. 4b, the cover layer 9 is thus in particular through to the base layer 2

Capillary forces “sucked in” so that this distance no longer exists and the fleas of the structural elements 13e define the fleas of the flow channel 4.

3 shows a cross-sectional view of a preferred embodiment of the microfluidic arrangement 1. The section runs, for example, along a line AA in FIG. 1. The microfluidic arrangement comprises a, preferably rigid, base layer 2, which is constructed from a base layer 3 and one arranged thereon Cover layer 9. The cover layer 9 comprises a cover layer 10, a first lacquer layer 14 arranged on a surface of the side of the cover layer 10 facing the base layer 2, and a first adhesive layer 11 which is on a surface of the side of the first lacquer layer facing the base layer 2 14 is arranged. The first lacquer layer 14 has a structure element 13v in the form of a depression which is arranged on a surface of the side of the first lacquer layer 14 facing the base layer 2. After arranging the side of the cover layer 9, preferably lacquer layer 14, having the structural element 13v, on the base layer 2, preferably

Base layer 3, the structural element 13v essentially forms the flow channel 4. In the embodiment shown, the flow channel 4 furthermore has a plurality of structural elements 13e in the form of convex elevations. The structural element 13e is arranged on a surface of the side of the flow channel 4 opposite the base layer 2 so that preferably between the, the

Cover layer 9 facing side of base layer 2, preferably base layer 3, and the at least one structural element 13e in the embodiment shown in FIG. 2, a distance is formed in an unfilled state of the microfluidic arrangement. There are of course also designs conceivable in which the distance shown in unfilled condition does not exist. In a filled state shown in FIG. 4b, for example (on the basis of a structure that has been slightly modified there)

microfluidic arrangement, the cover layer 9 is “sucked” onto the base layer 2, in particular by capillary forces, in such a way that this distance is no longer present and the height of the structural elements 13e define the height of the flow channel 4.

Figures 4a and 4b. each shows a cross-sectional view of a preferred

Embodiment of the microfluidic arrangement 1 in the unfilled state (FIG. 4a) or after the introduction of a fluid F to be examined, for example in the form of a solution, a suspension or emulsion (FIG. 4b). The section runs, for example, along a line AA in FIG. 1. The microfluidic arrangement comprises a, preferably rigid, base layer 2, which is composed of a base layer 3 and a cover layer 9 arranged thereon. The cover layer 9 comprises a cover layer 10, one on top of one Surface of the first lacquer layer 14 'arranged on the side of the cover layer 10 facing the base layer 2, and a first adhesive layer 11 ^' which is arranged on a surface of the side of the first lacquer layer 14 'facing the base layer 2. The first adhesive layer 11 'forms at least one structural element 13e' in the form of an elevation, after arranging the, the

Structural element 13e 'having side of the cover layer 9, preferably lacquer layer 14', on the base layer 2, preferably base layer 3, the structural element 13e 'essentially forms the flow channel 4. The flow channel 4 also has several structural elements 13e in the form of convex in the embodiment shown Surveys on. The structural element 13e is arranged on a surface of the side of the flow channel 4 opposite the base layer 2, so that preferably between the side of the base layer 2, preferably the base layer 3 facing the cover layer 9, and the at least one structural element 13e in the diagram shown in FIG. 2, a distance is formed in an unfilled state of the microfluidic arrangement. Of course, designs are also conceivable in which the distance shown does not exist in the unfilled state. In a filled state of the microfluidic arrangement, shown for example in FIG. 4b, the cover layer 9 is thus in particular through to the base layer 2

Capillary forces “sucked in” so that this distance no longer exists and the height of the structural elements 13e define the height of the flow channel 4. As shown in FIG. 4b, in the presence of a fluid F to be examined, the flexible cover layer 9 is "sucked" onto the at least one base layer 2, preferably by capillary pressure, so that between the at least one structural element 13e and the side facing the cover layer 9 the base layer 2, preferably the base layer 3, there is no gap and the at least one structural element 13e comes into direct contact with the base layer 2, preferably the base layer 3.

As a result, a defined distance between the layers is generated and thus also a defined volume of the flow channel 4.

The adhesive layer 11 ‘preferably has a thickness which is the height of the

Structural element 13e corresponds, preferably from a range from 0.2 pm to 500 pm, preferably from a range from 0.15 pm to 270 pm, preferably from a range from 0.2 pm to 170 pm, preferably from a range from 0, 5 pm to 100 pm, more preferably from a range from 0.65 pm to 75 pm, more preferably from a range from 0.75 pm to 55 pm, more preferably from a range from 0.85 pm to 35 pm, more preferably from a range from 0.95 pm to 20 pm, in particular from a range from 1 pm to 10 pm.

As described above, this direct contact further preferably leads to a changed brightness of the at least one structural element 13e in transmitted light. The change in the brightness of the at least one structural element 13e in transmitted light can serve as a reference or as a measuring element as to whether the desired height of the at least one flow channel 4, which preferably corresponds to the height of the at least one structural element 13e, has been set.

The base layer 2, preferably the base layer 3, is shown in FIGS. 1 to 4b

preferably composed of at least one polymer and / or at least one glass and / or at least one metal and / or at least one semiconductor material or a combination thereof.

Figures 5a and 5b each show a cross-sectional view of a preferred one

Embodiment of a transfer film 15 used in the method according to the invention comprising a first carrier layer 20 and one arranged thereon

Transfer layer 17. After applying the transfer film 15 with the from Transfer layer 20 facing away from the transfer layer 17 on a base layer 2 and subsequent removal of the transfer layer 20, the transfer layer 17 preferably forms the cover layer 9 of the microfluidic arrangement 1.

The carrier layer 20 preferably comprises a first carrier film 21 and a first release layer 22 arranged on the side facing the transfer layer 17.

The transfer layer 17 of the transfer film 15 used according to the invention preferably has the elements of the cover layer 9 described above by way of example in FIGS. 2, 3 and 4a, the elements of the cover layer 9, for example cover layer 10, first lacquer layer 14, 14 'and first adhesive layer 11, 1 T and structural elements 13v, 13e, 13e 'by sequentially arranging the corresponding layers on one side of the first carrier layer 20, preferably the side of the first release layer 22 facing away from the first carrier film 21, and below

Use of appropriate application and / or molding processes for producing the structural elements are provided.

The transfer film 15 shown by way of example in FIG. 5 a preferably has a cover layer 10 arranged on the side of the first release layer 22 facing away from the first carrier film 21. A first lacquer layer 14 ′ is preferably also arranged on the side of the cover layer 10 facing away from the first carrier layer 20.

For example, the cover layer 10 can be formed from a PET film with a thickness of 23 μm, onto which a coating of a printed and / or poured and / or knife-coated and / or sprayed, preferably radiation-curing or thermoplastic, first lacquer layer 14 'with a thickness of 8 μm is arranged.

Structural elements 13e, for example, are arranged on a surface of the side of the first lacquer layer 14 facing away from the first carrier layer 20

preferably have a distance of approximately 50 μm from the next structural element 13e in each direction in the plane. It is more preferred

sufficient if the minimum distance between two structural elements 13e approximately twice to four times the thickness of the, in particular multilayer, flexible transfer layer 17.

At least one structural element 13e and / or 13v is preferably arranged on a surface of the side of the first lacquer layer 14, 14 ′ facing away from the first carrier layer 20 by molding the at least one

Structural element 13e, for example, using a molding tool, for example a printing roller or embossing roller or replication tool, and subsequent curing of the first lacquer layer 14, 14 ', which is designed as a UV-curable lacquer layer, by electromagnetic radiation, for example UV radiation.

A UV-curable lacquer can be adjusted to be particularly flowable so that it can completely fill even the narrowest cavities of the printing roller or embossing roller or replication tool. The UV-curable lacquer can be cured directly by UV light, which is passed through the back of the cover layer 10, for example. The UV-curable lacquer can be applied over the entire surface or only to a limited extent and can be cured through the back of the cover layer 10 or through a transparent pressure roller.

The UV-curable lacquer can be, for example, one of the following lacquers: Monomers or oligomeric polyester acrylates, polyether acrylates, urethane acrylates or epoxy acrylates and amine-modified polyester acrylates, amine-modified polyether acrylates or amine-modified urethane acrylates.

However, it can also be provided that the paint is the first

Lacquer layer 14, 14 'is, in particular, an at least partially dried thermoplastic lacquer that is replicated under pressure and temperature. It can be, for example, a paint with the following composition:

Part of weight parts

Methyl ethyl ketone 400

Ethyl acetate 260 Butyl acetate 160

Polymethyl methacrylate (softening point approx. 170 ° C) 150

Preferably after the lacquer layer 14, 14 'has hardened, the first adhesive layer 11, 11' is applied to at least partial areas of a surface of the side of the first lacquer layer 14, 14 'facing away from the first carrier layer 20.

The transfer film 15 shown by way of example in FIG. 5b has the carrier layer 20 and a transfer layer 17 arranged thereon comprising a cover layer 10 and at least one structural element 13v in the form of a depression which is attached to a

Surface of the side of the cover layer 10 facing away from the first carrier layer 20 is arranged. More preferably, the cover layer 10 has at least one

Structural element 13e in the form of an elevation, which are arranged on a surface of the recess formed by the structural element 13v.

For example, cover layer 10 can be made of a thermoplastic film,

for example a PET film with a thickness of 30 μm, into which at least one structural element 13v is arranged, preferably introduced. Introducing at least one structural element 13v into a surface of one side of the

Cover layer 10 and preferably of the at least one structural element 13e can, for example, take place under pressure and temperature.

Preferably after arranging the at least one structural element 13v and more preferably the at least one structural element 13e, the first adhesive layer 11 is applied to at least partial areas of a surface of the side of the cover layer 10 facing away from the first carrier layer 20, preferably to at least partial areas of a surface of the at least one structural element 13v.

In a further embodiment, the cover layer 10 can be in the form of a printed and / or cast and / or knife-coated and / or sprayed, preferably radiation-curing or thermoplastic,

Lacquer layer can be applied to the first carrier layer 20, preferably carrier film 21. Subsequently, the first carrier layer 20 on the opposite side of the applied lacquer layer, at least one structural element 13v is introduced, for example by molding, and the applied and molded lacquer layer, for example by exposure to electromagnetic radiation, cured, preferably crosslinked, to obtain transfer film 15.

The cover layer 10 preferably consists of a lacquer, in particular a thermoplastic lacquer or a UV-curable lacquer, in a layer thickness of 0.5 μm to 500 μm.

In a preferred embodiment, the cover layer 10 can also consist of a thin PET carrier which is provided with a UV-curable lacquer 22 and which is laminated to the first carrier film 21 without bubbles.

It is also possible to make the cover layer 10 locally on the surface

to build different materials by printing different areas. It is particularly advantageous to apply different materials in register to different areas of the microfluidic

Arrangement. As a result, the optimal combinations of material and the at least one structural element 13v can be implemented locally in a cover layer 10.

In general, it can be provided that the applied lacquer is dried or cured, for example by thermal radiation or by contact with a heated body, for example a rotating roller, or by high-energy radiation, in particular UV radiation. A drying roller can be provided in order to form the cover layer 10 with a particularly smooth rear side. When using UV-curable lacquer, the curing of the

Structural layer can be carried out particularly easily through a transparent roller or from that side of the carrier film 21 facing away from the cover layer 10.

It can also be provided that the cover layer 10 is included by UV curing

to train location-dependent refractive index. The necessary pattern Irradiation can be generated, for example, by masks arranged between the radiation source and the structure layer or by the master relief structure. Furthermore, the cover layer 10 can be formed with a predetermined refractive index, for example in order to set the optical properties of an analysis element 12 arranged in the cover layer 10. A refractive index between 1.4 and 1.7 is advantageously provided if the cover layer 10 is applied, for example, to a polymer base layer or to optical glass as the base layer.

Furthermore, it can be provided that the cover layer 10 is designed to be particularly resistant to mechanical and / or chemical stresses and / or to be hydrophobic.

A particularly mechanically resistant UV-curing lacquer can have the following composition:

Part of weight parts

Methyl ethyl ketone 30

Ethyl acetate 20

Cyclohexanone 5

Polymethyl methacrylate 18

(MW 60000 g / mol)

Dipentaerythritol pentaacrylate 25

Photoinitiator (e.g. Irgacure 1000 from Ciba Geigy) 2 A UV-curing hydrophobic lacquer is obtained with the following composition:

Part of weight parts

Methyl ethyl ketone 28

Ethyl acetate 20

Cyclohexanone 5

Polymethyl methacrylate 18 (MW 60000 g / mol)

Dipentaerythritol pentaacrylate 25

Photoinitiator (e.g. Irgacure 1000 from Ciba Geigy) 2

Polysiloxane resin 2

The release layer 22 shown in FIG. 5a and / or FIG. 5b is preferably a UV-activatable adhesive. The adhesive that can be used for the release layer 22 has the following composition, for example:

Dicyclopentyloxyethyl methacrylate 50-60%

2-flydroxyethyl methacrylate 8%

Trimethylolpropane triacrylate 40 - 30%

(3- (2,3-epoxypropoxy) propyl) trimethoxysilane 1%

Irgacure 184 (CIBA) 1 - 2%

The release layer 22 is applied to the carrier film 21 in a layer thickness of 0.1 μm to 10 μm by means of a printing process, by means of casting or by means of a doctor blade.

At least one release layer 22 is preferably first applied to the first carrier layer 20, preferably carrier film 21. As described above, the cover layer 10 is subsequently applied to the applied release layer 22 in the form of a printed and / or poured and / or knife-coated and / or sprayed, preferably radiation-curing, lacquer layer.

Subsequently, at least one structural element 13v is inserted into the surface of the side of the applied lacquer layer opposite the release layer 22

introduced, for example by molding, and the applied and molded varnish layer, for example by the action of electromagnetic radiation, cured, preferably crosslinked, while obtaining a cover layer 10.

In an alternative embodiment, the top layer 10 is first

Lacquer layer 14, 14 'applied, for example by printing, pouring on,

Squeegee. Thereafter, in the surface of the cover layer 10 facing away On the side of the applied lacquer layer 14, 14 ', at least one structural element 13v is introduced, for example by molding, and the applied and molded lacquer layer is cured, preferably crosslinked, for example by the action of electromagnetic radiation. Preferably after the lacquer layer 14, 14 'has hardened, the first adhesive layer 11, 11' is applied to at least one

Subregions of a surface of the side of the first lacquer layer 14, 14 'facing away from the cover layer 10. The carrier film 21 with the release layer 22 arranged on the carrier film 21 or the cover layer 10 is then applied to the side of the cover layer 10 facing away from the lacquer layer 14, 14 ′. The release layer is arranged between the carrier film 21 and the cover layer 10.

6a shows a transfer film 15 'comprising a first carrier layer 20' and a transfer layer 17 'arranged thereon. The transfer layer 17 'comprises a cover layer 10', a lacquer layer 14 "arranged on the side of the cover layer 10 'facing away from the first carrier layer 20', as well as a plurality of structural elements 13e arranged on a surface of the side of the lacquer layer 14" remote from the first carrier layer 20 ' . A first adhesive layer 1T is also arranged on partial areas of a surface of the side of the lacquer layer 14 ″ facing away from the first carrier layer 20 ′.

The transfer film 15 ′ has at least two first partial areas 30 and, preferably a second partial area 31 enclosing the first partial areas 30. The first partial areas 30 here represent the part of the transfer film 15 ′ which is preferably to be transferred as a transfer layer 17 ′ to a base layer 2.

The first carrier film 21 is preferably a PET, PEN or BOPP film with a thickness of 6 μm to 125 μm. The release layer 22 is first applied to the first carrier film 21. The release layer 22 is made

for example made of a waxy material which is softened in particular by the heat occurring during a hot stamping process and enables the transfer layer 17 'to be reliably separated from the first carrier layer 20'. The thickness of the release layer 22 is preferably between 0.01 μm and 1.2 μm. The release layer 22 is preferably a UV-activatable adhesive, which more preferably has the composition indicated above. Release layer 22 is preferably applied to carrier film 21 by means of a printing process, by means of casting or by means of a doctor blade.

A protective lacquer layer can then be applied in a layer thickness between 0.5 gm and 1.5 gm. It is also possible that the

Protective lacquer layer takes over the function of release layer 22 and accordingly enables both the transfer layer 17 'from the carrier layer 20' and the transfer layer 17 'from mechanical influence

Protects against environmental influences. It is also possible that the protective lacquer layer is colored or contains micro- and nano-particles.

The cover layer 10 'can be designed as a replication lacquer layer, made of a thermoplastic lacquer in which structural elements 13e are molded by means of heat and pressure by the action of an embossing tool. Furthermore, it is also possible that the cover layer 10 'is formed by a UV-crosslinkable lacquer and the surface structure is shaped into the cover layer 10' by means of UV replication.

As described above, the top layer 10 'can be applied in the form of a printed and / or poured and / or knife-coated and / or sprayed, preferably radiation-curing, lacquer layer.

The cover layer 10 'preferably has a layer thickness between 0.5 μm and 500 μm. The at least one structural element 13e molded into the cover layer 10 'preferably has a distance of approximately 10 μm to 200 μm, preferably 15 μm to 90 μm, from the next structural element in each direction. The distances in different directions can also be different.

Preferably after the cover layer 10 'has hardened, a first adhesive layer 11 in a layer thickness of approximately 0.1 μm to 1 μm is applied to partial areas of the surface of the side of the cover layer 10 ′ opposite the release layer 22

arranged. The first adhesive layer 11 preferably consists of a thermally activated adhesive. A first area of the release layer 22 is then activated by exposure. For this purpose, the transfer film 15 ′ shown in FIG. 6 a is exposed to UV light in the area 30. For this purpose, a collimated light source can be used which is spaced apart on the side of the first carrier film 21 facing away from the transfer layer 17 ′ and from the first carrier film 21. In the beam path between the light source and the release layer 22 there is preferably an exposure mask

arranged, which covers the area 31 and thus enables a selective exposure of the area 30. The exposure source and the exposure mask are preferably part of a drum exposure unit over which the transfer film 15 'is guided.

In the area 31, the release layer 22 is not exposed to UV light and is therefore not activated.

The transfer layer 17 ′ and the first release layer 22 are then severed along the border lines defining the first partial areas 30 and separating the first partial areas 30 from the second partial area 31. These layers are preferably cut through by means of a punch.

It is also possible here for the punching depth to be selected such that the first carrier film 21 is also partially severed, for example in 20% to 80% of its thickness.

After severing, the part of the transfer layer 17 ′ comprising the second partial area 31 is peeled off from the first carrier film 21, the transfer layer 17 ′ remaining adhered to the first carrier film 21 in the first partial regions 30 due to the release layer 22 activated in the region 31 Obtaining a modified transfer film 15 ″ shown in FIG. 6b.

As shown in FIG. 6 b, residues of the non-activated material of the release layer 22 can remain in the region 31 on the first carrier film 21. Possibly. the film is re-exposed. After tightening the partial areas not to be transferred, the modified transfer film 15 ″ shown in FIG. 6 b results, which can be used for applying at least one transfer layer 17 ′ to a base layer 2. For this purpose, as shown in FIG. 6c, the modified transfer film 15 ″ is placed on the base layer 2 and the first adhesive layer 1 T is activated in a first partial area, for example by a correspondingly shaped hot stamping stamp 71.

Subsequently, the modified transfer film 15 ″ comprising the first carrier film 21 and release layer 22 is peeled off from the applied area of the transfer layer 17 ′, which remains on the base layer 2, so that preferably on at least a partial area of the, on the surface of at least one side of the

Transfer layer 17 'arranged at least one structural element 13e, 13e ‘at least a partial area of the at least one base layer 2 is arranged with at least partial formation of at least one, at least partially completely covered flow channel 4.

Typically, about 2 ml to 50 ml of venous or arterial blood are taken under laboratory conditions. This becomes an aliquot or aliquant part, if necessary after dilution and / or addition of reagents or separation of

Components, e.g. by centrifugation, filled into the inlet area of the microfluidic arrangement.

The amount of filled blood depends on the volume of the inlet and, if applicable, the outlet area and the actual examination chamber. A typical value for a 4 pm high examination chamber with a base area of 200 mm ² (10 mm x 20 mm) is around 0.8 mI (mI = microliter). A typical value for the inlet chamber is, for example, 0.5 ml to 10 ml, so that in this example approx. 1.3 ml to 10.8 ml were filled.

After filling, you waited about 10 seconds to 300 seconds for the

Examination chamber was filled or largely filled with the blood to be examined due to the capillary action. The filling process and the flow behavior of the blood in the chamber were followed visually. A control is also possible of the filling process by means of a camera, if necessary with saving the electronic

Image information in a storage device or on a storage medium.

The microfluidic arrangement can, in addition to the unambiguous assignment and / or identification and / or tracking, one or more barcodes and / or

Have labels and / or RFID elements.

When checking the filling process, it was usually also determined whether the filling process corresponded to predetermined criteria, for example whether a bubble-free filling, or only bubbles below a defined amount and / or number, certain formation of the liquid front, speed of the liquid front, e.g. homogeneous distribution of the fluorescence signals or fluorescence signals in the expected local area, fluorescence intensity, fluorescence spectrum, etc.

took place.

The evaluation was initially carried out visually. Alternatively, a

Evaluation take place using automated image evaluation devices. Machine algorithms, in particular self-learning machine algorithms, which algorithms improve themselves in particular through recursion and / or expand their function, can also be used.

The observation, image acquisition and / or evaluation can take place outside of the measuring device or the measuring arrangement as well as within the measuring arrangement. The result of the evaluation was documented in each case. If the criteria were not met, the measurement was canceled manually or automatically.

This was followed by the actual image acquisition of the sample within the sample chamber to examine, for example, the specific number and / or the shape of the blood components, for example the specific shape of

Sickle cells and / or the presence of DNA in cells and / or the

Absence of certain blood components and / or the ratio of the number of different blood components to one another, in particular blood cells, in the sample chamber. Furthermore, specific staining methods can also be used, such as, for example, the Giemsa staining known to the person skilled in the art, which serves to differentiate between different cell types. The one used for this

Giemsa solution consists of a mixture of the dyes azure A eosinate, azure B eosinate, methylene blue eosinate and methylene blue chloride in methanol with glycerine as a stabilizer.

Further histological stains and / or reactions are known to the person skilled in the art.

Depending on the task at hand, specific

Lighting methods are used. Illumination using monochromatic light or light from a special spectral range or

Combinations of these.

The illumination can take place in incident light and / or in transmitted light. It is also possible to switch various lights on and off at different positions and / or to vary the lighting positions (moving the lighting, bright field, dark field). Illumination from a lateral position (flat angle between 60 ° and 0 ° with respect to the horizontal or horizontal) e.g. for creating shadow images etc. are possible. The image acquisition can take place by means of high-resolution cameras, microscopes with built-in / attached cameras or also through direct contact with an image chip (image acquisition without imaging components). The image acquisition takes place in the range of the wavelength of the incident light and / or, if the emitted light has a different wavelength than the incident light (e.g. by using materials as an upconverter and / or downconverter), at the wavelength or the wavelengths of the emitted light.

In the case of microscopes, a technique is preferably used in which partial images of the sample chamber are first recorded, which are then captured via

Image editing programs can be combined to form an overall image. The observation and / or the evaluation can also be carried out by trained personnel using microscopy. In the blood analysis, for example, the specific number and / or the shape of the blood components, for example the specific shape of sickle cells and / or the presence of DNA in cells and / or the absence of certain blood components and / or the ratio of the number, are different

Blood components to each other, in particular recorded by blood cells. The

Blood components can be stained, for example, with fluorescent dyes.

An image evaluation then takes place, possibly with a comparison of images

different recording techniques / lighting according to methods known to the person skilled in the art.

The result of the evaluation was documented and output as an analysis result in analog or digital form. Possibly. the results are also encrypted or unencrypted on locally available or remote

Display devices, in particular transmitted via networks (wireless, wired).

Analysis chambers that are not completely filled, areas with microstructures, air bubbles can be recorded in appropriate evaluation processes and taken into account in the evaluation.

After the analysis, the microfluidic arrangement, together with the sample contained therein, was properly disposed of.

List of reference symbols

F fluid to be examined

1 microfluidic arrangement

2 base position

3 base layer

4 flow channel

9 top layer

10, 10 'top layer

1 1, 1 1 'first layer of adhesive

13e, 13e ‘structural element (elevation) 13v structural element (depression)

14, 14 ‘, 14“ first layer of lacquer 1 5 1 5 1 5 transfer film

17, 17 'transfer position

20, 20 'first carrier layer

21 first carrier film

22 first release layer

30 first area

31 second area

41 inlet

42 outlet

71 hot stamping dies

Claims

1. A method for producing a microfluidic arrangement (1) comprising at least one, at least partially completely covered

Flow channel (4) in fluid communication with at least one inlet (41) and at least one outlet (42), the method comprising the following steps: a) providing at least one base layer (2),

b) providing at least one flexible cover layer (9), comprising at least one structural element (13e, 13e ‘, 13v) which is arranged on a surface of at least one side of the cover layer (9), and

c) Arranging the at least one flexible cover layer (9) on at least a partial area of the at least one base layer (2), so that on at least a partial area of the at least one structural element (13e, 13e arranged on the surface of at least one side of the cover layer (9) e ', 13v) at least a partial area of the at least one base layer (2) is arranged to form at least one flow channel (4) which is completely covered at least in areas.

2. The method according to claim 1,

characterized,

that the at least one base layer (2) is rigid.

3. The method according to any one of claims 1 or 2

characterized,

that the at least one, preferably rigid, base layer (2) has a thickness of at least 200 μm, preferably of at least 600 μm.

4. The method according to any one of the preceding claims,

characterized,

that the at least one, preferably rigid, base layer (2) has a modulus of elasticity of greater than 1000 N / mm ² , determined in accordance with DIN EN ISO 527-3 (issue date: 2003-07), preferably at room temperature.

5. The method according to any one of the preceding claims,

characterized,

that the at least one, preferably rigid, base layer (2) at least

is partially transparent to electromagnetic radiation, preferably in a wavelength range of the electromagnetic radiation from 200 nm to 1000 nm.

6. The method according to any one of the preceding claims,

characterized,

that the at least one, preferably rigid, base layer (2) is composed of at least one polymer, at least one glass, at least one metal, at least one semiconductor material or a combination thereof.

7. The method according to any one of the preceding claims,

characterized,

that the at least one, preferably rigid, base layer (2) is a CCD sensor or a CMOS sensor.

8. The method according to any one of the preceding claims,

characterized,

that the at least one, preferably rigid, base layer (2) has macroscopic structures with a minimum structure size greater than 10 μm, preferably inlet, outlet, opening, depression, bulge,

Wall element, channel element, antechamber, mixing chamber, collecting chamber, analysis chamber or combinations thereof.

9. The method according to any one of the preceding claims, characterized,

that the at least one, preferably rigid, base layer (2) has at least one

Has decorative element, wherein the at least one decorative element the

Surface texture and / or the color of the surface of the at least one

Base layer (2) influences, wherein the at least one decorative element is preferably designed as a motif, as a decoration, for example single image decoration or continuous decoration, as a pattern, or a combination thereof.

10. The method according to claim 9,

characterized,

that the at least one decorative element is at least partially designed as a decorative layer, which is preferably selected from the group consisting of transparent and / or colored lacquer layers, in particular comprising one or more dyes and / or pigments, replication layers with molded optically active

Surface structure, reflective layers, especially opaque

Reflective layers, transparent reflective layers, metallic

Electrode layers, magnetic layers, magnetic storage layers and

Combinations thereof is selected.

11. The method according to any one of the preceding claims,

characterized,

that the at least one flexible cover layer (9) has a maximum thickness of at most 250 μm, preferably at most 100 μm.

12. The method according to any one of the preceding claims,

characterized,

that the at least one flexible cover layer (9) has a modulus of elasticity - tensile strength of 100 MPa to 4000 MPa, in each case determined according to DIN ISO 527 Part 3 (date of issue: 2003-07), preferably determined at room temperature.

13. The method according to any one of the preceding claims,

characterized,

that the at least one flexible cover layer (9) comprises a cover layer (10, 10) made of at least one replication lacquer, the at least one structural element (13e, 13e ‘, 13v) on a surface of at least one side of the cover layer (10,

10 ‘) is arranged.

14. The method according to any one of the preceding claims,

characterized,

that on the side of the cover layer (10, 10) having at least one structural element (13e, 13e, 13v), at least one first adhesive layer (11, 11 ') is arranged.

15. The method according to any one of the preceding claims,

characterized,

that the at least one flexible cover layer (9), furthermore at least one

Has decorative element, wherein the at least one decorative element the

Surface texture and / or the color of the surface that influences at least one flexible cover layer, the at least one decorative element preferably being designed as a motif, as a decoration, for example single image decoration or endless decoration, as a pattern, or a combination thereof.

16. The method according to claim 15,

characterized,

Surface structure, reflective layers, especially opaque

Reflective layers, transparent reflective layers, metallic

Volume hologram layers, liquid crystal layers, in particular cholesteric liquid crystal layers, electrically conductive layers, antenna layers, Electrode layers, magnetic layers, magnetic storage layers and

Combinations thereof is selected.

17. The method according to any one of the preceding claims,

characterized,

that the at least one structural element (13e, 13e ‘, 13v) has a height of at most 500 pm, preferably from a range from 0.1 pm to 500 pm.

18. The method according to any one of the preceding claims,

characterized,

that the at least one structural element is formed from at least one raised element (13e, 13e ‘) on a surface of the flexible cover layer (9) and / or from at least one recess (13v) on a surface of the flexible cover layer (9).

19. The method according to any one of the preceding claims,

characterized,

that the at least one flexible cover layer (9), furthermore at least one

Has analysis element that preferably includes all structural elements required for later use.

20. The method according to any one of the preceding claims,

characterized,

that the at least one flexible cover layer (9) at least regionally,

preferably in an area comprising at least one analysis element which is transparent to electromagnetic radiation, preferably in a range of the wavelength of the electromagnetic radiation from 200 nm to 1000 nm.

21. The method according to any one of the preceding claims,

characterized,

that the at least one analysis element continues to have at least one

Functional element comprising at least in fluid communication with the

at least one channel is arranged and preferably from the group consisting of microfluidic separators, microfluidic mixers, microfluidic pumps, microfluidic valves, and combinations thereof.

22. The method according to any one of the preceding claims,

characterized,

that the at least one flexible cover layer (9) further comprises at least one additive, which is preferably selected from the group consisting of water repellants, dyes, contrast agents, stabilizers, light stabilizers, antioxidants, biological auxiliaries, surfactants and mixtures thereof.

23. The method according to claim 22,

characterized,

that the at least one additive is soluble in and / or on the top layer (9),

preferably cover layer (10, 10 ‘), is arranged, preferably on or on at least partial areas of at least one surface of the at least one

Structural element (13e, 13e ‘, 13v).

24. The method according to any one of claims 22 or 23,

characterized,

that the at least one additive is arranged in at least one reservoir that is preferably in fluid connection with the at least one structural element (13e, 13e, 13v).

25. The method according to any one of claims 22 to 24,

characterized,

that the at least one additive is arranged in at least one first lacquer layer (14, 14 ‘, 14"), the at least one first lacquer layer (14, 14 ‘, 14")

preferably has at least one structural element (13e, 13v).

26. The method according to any one of the preceding claims,

characterized,

that the at least one cover layer (9) is provided in the form of a transfer film (15, 15 ', 15 "), wherein the transfer film (15, 15', 15") furthermore has at least one first carrier layer (20) which is the at least one structural element (13e, 13e ”, 13v) opposite side of the at least one cover layer (9) is detachably arranged.

27. The method according to claim 26,

characterized,

that the at least one first carrier layer (20, 20 ') comprises at least one first carrier film (21) made of a polyester, a polyolefin or a combination thereof, in particular of PET, which preferably has a layer thickness between 4 μm and 100 μm, preferably between 10 pm and 50 pm.

28. The method according to any one of claims 26 or 27,

characterized,

that the at least one first carrier layer (20, 20 ‘) further comprises at least one first release layer (22) which is arranged on the side of the first carrier layer (20, 20‘) facing the cover layer (9).

29. The method according to claim 28,

characterized,

that the at least one first release layer (22) is at least one wax,

preferably montan ester wax, at least one silicone, at least one

Polyurethane or a combination thereof, preferably in one

Layer thickness from 0.1 nm to 100 nm.

30. The method according to any one of claims 1 to 25,

characterized,

that the at least one cover layer (9) is provided in the form of a laminating film, the laminating film furthermore having at least one carrier layer which is located on the side of the at least one cover layer (9) opposite the at least one structural element (13e, 13e ', 13v), is preferably not detachable, arranged.

31. The method according to claim 30,

characterized,

that the laminating film further comprises at least one second adhesive layer, which is arranged on the side of the carrier layer (20, 20 ') facing the cover layer (9).

32. The method according to any one of the preceding claims,

characterized,

that on the side of the cover layer (9) containing the at least one structural element (13e, 13e ', 13v), a protective layer is furthermore detachably arranged, which preferably before the arrangement of the at least one cover layer (9) on the base layer (2) of the top layer (9) is removed.

33. The method according to any one of the preceding claims,

characterized,

that in step c) the at least one, preferably rigid, base layer (2) is permanently arranged on the cover layer (10).

34. Microfluidic arrangement (1) comprising at least one, at least partially completely covered flow channel (4) in fluid connection with at least one inlet (41) and at least one outlet (42), preferably produced by a method according to one of claims 1 to 33,

characterized,

that the microfluidic arrangement (1) comprises at least one base layer (2) and at least one flexible cover layer (9) comprising at least one, on one

Surface of at least one side of the cover layer (9) arranged structural element (13e, 13e ', 13v), and wherein on at least a portion of the, on the surface of at least one side of the cover layer (9) arranged at least one structural element (13e, 13e', 13v) at least a partial area of the at least one base layer (2) is arranged with at least partial formation of the at least one flow channel (4) which is at least partially completely covered.

35. Microfluidic arrangement (1) according to claim 34,

characterized,

that the at least one base layer (2) is rigid.

36. Microfluidic arrangement (1) according to one of claims 34 or 35, characterized in that that the at least one, preferably rigid, base layer (2) has a thickness of at least 200 gm, preferably at least 600 gm.

37. Microfluidic arrangement (1) according to one of claims 34 to 36, characterized in that

that the at least one, preferably rigid, base layer (2) has a modulus of elasticity greater than 1000 N / mm ² , determined in accordance with DIN ISO 527 Part 3 (issue date: 2003-07), preferably at room temperature.

38. Microfluidic arrangement (1) according to one of claims 34 to 37, characterized in that

that the at least one, preferably rigid, base layer (2) at least

39. Microfluidic arrangement (1) according to one of claims 34 to 38, characterized in that

40. Microfluidic arrangement (1) according to one of claims 34 to 39, characterized in that

41. Microfluidic arrangement (1) according to one of claims 34 to 40, characterized in that

42. Microfluidic arrangement (1) according to one of claims 34 to 41, characterized in that

that the at least one, preferably rigid, base layer (2) has at least one

Has decorative element, wherein the at least one decorative element the

Surface texture, and / or the color of the surface, which influences at least one, preferably rigid, base layer (9), the at least one

43. Microfluidic arrangement (1) according to claim 42,

characterized,

Surface structure, reflective layers, especially opaque

Reflective layers, transparent reflective layers, metallic

Electrode layers, magnetic layers, magnetic storage layers, and combinations thereof.

44. Microfluidic arrangement (1) according to one of claims 34 to 43, characterized in that

that the at least one, preferably rigid, base layer (2) at least

45. Microfluidic arrangement (1) according to one of claims 34 to 44, characterized in that that the at least one flexible cover layer (9) has a maximum thickness of at most 100 gm, preferably at most 50 gm.

46. Microfluidic arrangement (1) according to one of claims 34 to 45, characterized in that

that the at least one flexible cover layer (9) has a modulus of elasticity - tensile strength of 100 MPa to 4000 MPa, in each case determined in accordance with DIN ISO 527 Part 3 (issue date: 2003-07), preferably at room temperature.

47. Microfluidic arrangement (1) according to one of claims 34 to 46, characterized in that

that the at least one flexible cover layer (9) comprises a cover layer (10, 10 ') made of at least one, preferably cured, replication lacquer, the at least one structural element (13e, 13e', 13v) on a surface of at least one side of the cover layer (10 , 10 ') is arranged.

48. Microfluidic arrangement (1) according to one of claims 34 to 47, characterized in that

that between the flexible cover layer (10, 10 ‘) and the base layer (2) at least one first adhesive layer (11, 1 T) is arranged.

49. Microfluidic arrangement (1) according to one of claims 34 to 48, characterized in that

that the at least one flexible cover layer (9), furthermore at least one

Has decorative element, wherein the at least one decorative element the

Surface texture, and / or the color of the surface that influences at least one flexible cover layer (9), the at least one decorative element preferably being designed as a motif, as a decoration, for example single image decoration or endless decoration, as a pattern, or a combination thereof.

50. Microfluidic arrangement (1) according to claim 49,

characterized,

that the at least one decorative element is at least partially designed as a decorative layer, which is preferably from the group consisting of transparent and / or colored lacquer layers, in particular comprising one or more dyes and / or pigments, replication layers with molded optically active

Surface structure, reflective layers, especially opaque

Reflective layers, transparent reflective layers, metallic

Electrode layers, magnetic layers, magnetic storage layers and

Combinations thereof is selected.

51. Microfluidic arrangement (1) according to one of claims 34 to 50, characterized in that

52. Microfluidic arrangement (1) according to one of claims 34 to 51, characterized in that

53. Microfluidic arrangement (1) according to one of claims 34 to 52, characterized in that

that the at least one raised structural element (13e, 13e ‘) is selected from a spherical segment, pyramid, cone, cylinder, prism, prismatoid, spherical layer,

Tapered cone, irregular body, and combinations thereof.

54. Microfluidic arrangement (1) according to one of claims 34 to 53, characterized in that

that the at least one flexible cover layer (9), furthermore at least one

55. Microfluidic arrangement (1) according to one of claims 34 to 54, characterized in that

that the at least one flexible cover layer (9) at least regionally,

56. Microfluidic arrangement (1) according to one of claims 34 to 55, characterized in that

that the at least one analysis element continues to have at least one

Functional element comprising at least in fluid communication with the

at least one channel is arranged and is preferably selected from the group consisting of microfluidic separators, microfluidic mixers, microfluidic pumps, microfluidic valves, and combinations thereof.

57. Microfluidic arrangement (1) according to one of claims 34 to 56, characterized in that

that the at least one flexible cover layer (9) and / or the at least one

Base layer (2) furthermore comprises at least one additive which is preferably selected from the group consisting of flydrophobizing agents, dyes, contrast agents, stabilizers, light stabilizers, antioxidants, biological auxiliaries, surfactants and mixtures thereof.

58. Microfluidic arrangement (1) according to claim 57,

characterized,

that the at least one additive is detachably arranged in and / or on at least partial areas of at least one surface of the base layer (2).

59. Microfluidic arrangement (1) according to one of claims 57 or 58, characterized in that

that at least one additive is soluble in and / or on the base layer (2), preferably in / and or on at least partial areas of at least one surface of a

Base layer (2) is arranged and that at least one further additive is releasable in and / or on a second cover layer (9 '), and / or preferably in and / or on at least partial areas of at least one surface of a second base layer (2 ') is arranged.

60. Microfluidic arrangement (1) according to one of claims 57 to 59, characterized in that

that the at least one additive is detachably arranged in and / or on the cover layer (9), preferably cover layer (10, 10 ‘), preferably on or on at least partial areas of at least one surface of the at least one

Structural element (13e, 13e ‘, 13v).

61. Microfluidic arrangement (1) according to one of claims 57 to 60, characterized in that

that the at least one additive is arranged in at least one reservoir that is preferably in fluid connection with the at least one structural element (13e, 13e ‘, 13v).

62. Microfluidic arrangement (1) according to one of claims 57 to 61, characterized in that

that the at least one additive is arranged in at least one first lacquer layer (14, 14 ‘, 14"), the at least one first lacquer layer (14, 14 ‘, 14") preferably comprising at least one structural element (13e, 13v).

63. Microfluidic arrangement (1) according to one of claims 34 to 62, characterized in that

that the microfluidic arrangement (1) is designed as a cuvette.

64. Measuring system comprising at least one microfluidic arrangement (1) according to one of claims 34 to 63 and at least one detector.

65. The measuring system of claim 64 further comprising at least one

Radiation source.

66. Use of a microfluidic arrangement (1) according to one of claims 34 to 63 or of a measuring system according to one of claims 64 or 65 for the in- vitro investigation of human or animal body fluids, especially in in-vitro blood analysis.