DE102016213404A1 - Method for producing a fluidic device for a lab-on-chip system and fluidic device for a lab-on-chip system - Google Patents

Abstract

The approach presented here relates to a method for producing a fluidic device (100) for receiving at least one fluid (115) for a lab-on-chip system. The method comprises at least one molding step, one injection step, one filling step, one folding step, and one sealing step. In the step of molding, at least one chamber (135) is formed which is adapted to receive the fluid (115). The chamber (135) is thereby formed in a chamber region (125) of a composite film (105), which is arranged opposite a cover region (130) of the composite film (105). In the gating step, a chamber bottom outside of the chamber portion (125) is molded with a backing plate material to stabilize the at least one chamber (135). In the filling step, the at least one chamber (135) is filled with at least one fluid (115). In the flip-over step, the lid region (130) of the composite film (105) is folded over to close the at least one chamber (135). In the sealing step, the lid portion (130) is sealed to the chamber portion (125) in the region of the at least one chamber (135) to fluid-tightly seal the chamber (135).

Description

State of the art

The approach is based on a device or a method according to the preamble of the independent claims.

Microfluidic chips for lab-on-chip systems are used in combination with special evaluation devices for medical analysis and timely diagnostics in medical practices and hospitals. The various analysis chips each consist of a structured plastic carrier plate, intermediate plates and a plastic cover plate. Between the plates, the necessary functional components, such. As heat sources, sensors and sealed reagent chamber carrier for certain liquids introduced in additional bonding or welding processes.

The DE 10 2010 041 287 A1 describes a manufacturing process in which transparent fluid plates with intermediate layer and functional components are joined together by assembly injection molding.

Disclosure of the invention

Against this background, a method for producing a fluidic device for a lab-on-chip system according to the main claim are presented with the approach presented here. The measures listed in the dependent claims advantageous refinements and improvements of the independent claim device are possible.

A method for producing a fluidic device for receiving at least one fluid for a lab-on-chip system is presented. The method comprises at least one forming step, one injection step, one filling step, one folding step, and one sealing step. In the step of molding at least one chamber is formed, which is adapted to receive the fluid. The chamber is thereby formed in a chamber region of a composite film. In the injection step, a chamber bottom outside of the chamber portion is molded with a backing plate material to stabilize the at least one chamber. In the filling step, the at least one chamber is filled with the at least one fluid. In the folding-over step, a cover region of the composite film is folded over in order to close the at least one chamber, wherein the cover region is arranged in a different region of the composite film than the chamber region. In the step of sealing, the lid portion is sealed to the chamber portion in the region of the at least one chamber to fluid-tightly seal the chamber.

This method may be implemented, for example, in software or hardware or in a hybrid of software and hardware.

In the present case, a fluidic device can be understood to mean a device for storing one or more fluids, which can be used, for example, as a reagent in a lab-on-chip. A lab-on-chip system can be understood here to mean a system in which a small laboratory, ie. H. one or more reaction chambers and / or material storage chambers are arranged so that a laboratory field test can be performed on such a system even outside a laboratory building. In the present case, a chamber region may be understood as meaning a region of the composite film in or on which the chamber is to be formed. In the present case, the injection-molding can also include injection-molding of an element in an injection mold.

The method presented here can rapidly produce in a few simple steps a fluidic device which has a fluid-tight chamber and advantageously consists of only four components, namely the fluid-tight composite foil, the stable carrier plate material, the fluid and a sealed seam. The fluid is surrounded only by the composite film, the chamber of the composite film is particularly securely closed, since the same material is sealed on top of each other / was.

In order to ensure that the cover area can close the chamber in the folding-over step, in the step of molding, the at least one chamber can be formed in a chamber area of the composite film which essentially comprises one half of a surface of the composite film.

According to one embodiment, in the step of molding, a plurality of chambers may be formed in the chamber region of the composite film. Thus, the microfluidic device can store a plurality of fluids in a plurality of chambers.

In order to quickly and easily be able to mold the at least one chamber, the chamber can be formed in the step of molding by a deep-drawing process and / or a folding process.

If, in the step of molding, the at least one chamber is formed into a composite film which has at least partially an aluminum layer, this can ensure a fluid tightness of the composite film.

In the gating step, the lid portion of the composite foil may be fixed by a slider that seals the lid portion against the injecting backing plate material, which may be hot. In this case, a Teflon insert on the slider, which contacts the lid region and becomes soft at high temperatures of, for example, 100.degree. C. to 140.degree. C., can ensure, for example, that the composite film is not damaged.

The method may include a step of cooling in response to the step of molding, wherein in the cooling step, cooling and / or at least partial curing of the backing sheet material may be effected and / or awaited. Before filling the composite foil, it may be advantageous if the backing plate material has cured, as this then provides stability.

According to one embodiment, the lid region can be sealed to the chamber region in the sealing step by at least one U-shaped sealing seam, in particular that of a folding line, along which the lid region has been folded over, can be arranged opposite one another. Thus, a quadrangular chamber opening of the chamber covered by the lid region can be reliably sealed circumferentially around all four sides of the chamber opening in order to close the chamber in a fluid-tight manner. In this case, the opening of the U-shaped sealed seam facing the Umklapplinie.

In the step of injection molding, a carrier plate can be produced and / or injection-molded with at least one fluid channel. Through the fluid channel, the fluid can be directed out of the chamber in the region of the fluid channel after the composite film has been opened.

A fluidic device for receiving at least one fluid for a lab-on-chip system comprises at least one composite foil, a carrier plate, a fluid and a sealed seam. The composite film has a chamber portion and a lid portion folded onto the chamber portion, the chamber portion forming at least one chamber extending from the lid portion for receiving the fluid sealed by the lid portion. The support plate is mounted and / or molded on a chamber bottom outside of the chamber region facing away from the cover region, for example by means of an injection molding process, in order to stabilize the at least one chamber. The fluid is disposed in the chamber and the sealing seam seals the lid portion with the chamber portion in the region of the chamber such that the chamber is sealed fluid-tight.

A fluidic device presented here can serve as a substitute for known fluidic devices, with the difference that the device presented here realizes the already mentioned advantages of the method.

Embodiments of the approach presented here are shown in the drawings and explained in more detail in the following description. It shows:

1 a perspective top view of a fluidic device for a lab-on-chip system according to an embodiment;

2 a flowchart of a method for manufacturing a fluidic device according to an embodiment;

3 a perspective view of a composite film according to an embodiment; and

4 a cross section of a composite film with a support plate according to an embodiment.

In the following description of favorable embodiments of the present approach, the same or similar reference numerals are used for the elements shown in the various figures and similar acting, with a repeated description of these elements is omitted.

1 shows a perspective view of a fluidic device 100 for a lab-on-chip system according to an embodiment.

The device 100 has a composite foil 105 , a support plate 110 , at least one fluid 115 and at least one sealed seam 120 on. The composite foil 105 has a chamber area 125 and one on the chamber area 125 folded lid area 130 on. The lid area 130 is along a fold-over line 133 over the chamber area 125 worked out. The chamber area 125 according to this embodiment, four forms from the lid portion 130 away extending chambers 135 out through the lid area 130 are closed. According to an alternative embodiment, the chamber area 125 also only one chamber 135 molding. The carrier plate 110 is on one of the lid area 130 remote chamber bottom outside of the chamber area 125 molded and trained to the chambers 135 to stabilize. According to this embodiment, in each of the four chambers 135 a fluid 115 arranged. The device 100 also includes four sealed seams 120 covering the lid area 130 with the chamber area 125 in the area of the chambers 135 seal so that the chambers 135 sealed fluid-tight. According to this embodiment, the lid portion 130 and the chamber area 125 welded together.

According to this embodiment, the chamber area comprises 125 the composite foil 105 one half of a surface of the composite film 105 , According to this embodiment, the lid portion 130 with the chamber area 125 through four U-shaped sealing seams 120 sealed, with the U-shaped sealed seams 120 the Umklapplinie 133 are arranged opposite one another. According to this embodiment, the composite film 105 an aluminum layer, which is formed to the composite film 105 to make fluid tight.

In the following, details of the device already described are described 100 once more detailed: Shown here is a schematic diagram of a molded and welded reagent chamber area in the form of the device 100 ,

The approach described here makes it possible to develop a transparent and media-dense plastic microfluidic analysis chip according to this exemplary embodiment, its media-tight reagent chambers in the form of the chambers 135 during the manufacturing process directly into the carrier plate 110 to get integrated. Here is the chamber area 125 , which can also be referred to as chamber surfaces, made of the same material, for. As plastic, such as the sealing layer in the form of the lid area 130 to a media-tight weld, here the sealed seam 120 , to achieve. Due to the joining processes or the insertion of functional components, germs or dirt particles that can influence a measurement result must not get into the analysis chip. With only a few process steps, the analysis chip can be produced cost-effectively and with few sources of error in a short cycle time.

By applying or injecting the preformed composite film 105 is the structured carrier plate 110 directly with the chambers 135 connected media-tight in one production step. Advantageously, no additional process steps have been needed, such as injection molding of a particular reagent chamber component or sealing of different types of plastics. The composite foil 105 from according to this embodiment, aluminum and various plastic layers can by a deep-drawing process or a folding process according to the chamber geometry of the chambers 135 preformed and cut to size. The composite foil 105 was then placed on tempered cores in a 4 shown injection mold for the carrier plate 110 placed and held by a vacuum. The lid area 130 was thereby fixed by a slide, which with a soft Teflon insert against the melt of the support plate 110 seals. The carrier plate plastic in the form of a carrier plate material of the carrier plate 110 was then injected and the composite film 105 brought into a defined and stable form by the injection molding. An advantage of this is that in the selection of the carrier plate material requirements for corresponding barrier properties omitted, as this alone by the composite film used 105 To be defined. Commercially available composite films 105 usually have an aluminum layer as a diffusion barrier, the barrier properties of the chambers described here 135 higher than polymer-based reagent chambers or reagent containers. Thus, a long-term stable storage of fluids 115 possible on the analysis chip. After a given cooling time, the molded carrier plate was 110 with the composite foil 105 demoulded by ejector and in a filling system with the fluids 115 fed. Subsequently, the lid area 130 folded in a sealing facility and the chambers 135 each sealed on only three pages. Since the joining surfaces are made of the same plastic, on the one hand the seam strength is high and on the other hand a possible diffusion through an optimal sealing is reduced to a minimum. In contrast to known methods for producing fluidic devices, a production time, a logistics effort, a number of processes with sources of error and thus significantly a component price are reduced.

The carrier plate 110 may consist of a plastic, such as a thermoplastic, such. From PC and / or PA and / or PS and / or PP and / or PE and / or PMMA and / or COP and / or COC. The composite foil 105 can a commercial polymer composite film of polymeric sealant and protective layers of z. B. PE and / or PP and / or PA and / or PET and / or Lackkaschierung with a barrier layer of vapor-deposited aluminum and / or other high barrier layers such as EVOH and / or BOPP exist. An exemplary dimension of the carrier plate 110 has a thickness of the carrier plate 110 from 0.5 to 5 mm. A typical multilayer structure of the composite film 105 comprises a 5 μm to 500 μm thick barrier layer, for example of aluminum, a 5 μm to 500 μm thick sealing layer and a 5 μm to 500 μm thick protective layer. A volume of the chambers may comprise 100 to 10,000 μl.

2 shows a flowchart of a method 200 for producing a fluidic device according to an embodiment. This can be a procedure 200 for making the in 1 act described device.

The procedure 200 includes at least one molding step 205 , a step of gating 210 , a step of filling 215 , a step of flipping over 220 and a step of sealing 225 , Optionally, the method includes 200 here a step of cooling 230 ,

In the step of molding 205 At least one chamber is formed, which is adapted to receive a fluid. The chamber is thereby formed in a chamber region of a composite film, which is arranged opposite a cover region of the composite film. In the step of gating 210 For example, a chamber bottom outside of the chamber portion is sprayed or back-injected with a backing plate material to stabilize the at least one chamber. In the step of filling 215 the at least one chamber is filled with at least one fluid. In the step of flipping over 220 the lid region of the composite foil is folded over in order to close the at least one chamber. In the step of sealing 225 the lid region is sealed to the chamber region in the region of the at least one chamber in order to seal the chamber in a fluid-tight manner.

The step of cooling 230 becomes in this embodiment in response to the step of Anspritzens 210 executed, wherein in the cooling step 230 a cooling of the carrier plate material is effected.

The following describes details of the method already described 200 once more detailed: Shown is a method 200 for the production of media-tight reagent chambers in lab-on-chip systems by injection or injection molding of composite films and welding of identical surfaces. The procedure 200 can be used with all plastic microfluidic analysis chips with reagent chambers.

For the implementation of the procedure 200 will be in the first step 205 a deep-drawing press with a punching device or a folding station, for example a Tetra Pak folding station, required for the preforming of the composite film. At the second step 210 In an injection molding or injection-compression molding tool, the composite film is sprayed on or behind and at the same time the carrier plate is produced with fluid channels. A tool with a special slide design is installed in an injection molding machine for transparent plastics. In the first step 205 The composite film, for example, aluminum and polypropylene, short PP, layers, with a thickness between 0.2 and 0.8 mm from roll to roll through the deep drawing press and thereby preformed the chambers. Immediately thereafter, the contour of the required film geometry is punched out. According to a further advantageous embodiment, non-metallized composite films with high barrier properties, for. As Aclar, are used, which can be thermoformed at steeper angles and thus high aspect ratios and a minimum footprint, footprint, the chambers allow. Another possible variant is a production of the contour in the form of the chambers by the Tetra Pak folding technique of a composite film cutout. This has the particular advantage that with metallized composite films, which could break at steep angles in the deep-drawing process, also high aspect ratios of the chamber geometries can be achieved. Thus, a minimum space requirement of the chambers is achieved on the analysis chip here, too.

With a handling of the preform then as in 4 placed on tempered cores of a cavity and sucked by an applied vacuum. The protruding cover area is fixed by the slide with Teflon insert when closing the tool. Since the Teflon material softens at a mold temperature between 100 ° C and 140 ° C, the film can not be damaged and sealed well against the inflowing plastic melt. With an injection unit of the injection molding machine, the transparent plastic, for example polycarbonate, PC for short, is injected. By this An or Hinterspritzgießverfahren in the form of the step 210 The film preform is brought in the form of composite film in the defined shape and molded as a stable chamber.

After a given cooling time in the form of the step 230 the molded carrier plate is demoulded with the composite film by ejector and the chambers are in step 215 in a filling fluid, z. As reagents fed. The following are in a sealing system in step 220 the lid area folded down and in step 225 the chambers are sealed on only three sides. Since the joining surfaces are made of the same plastic, the seam strength increases. This results in media-tight reagent chambers in the form of the chambers, which are integrated stably and with reproducible geometries directly in the carrier plate for microfluidic chips.

In contrast, in known processes differently structured plastic plates are produced on injection molding machines in special injection molding tools or on hot stamping systems. The functional components used, such as, for example, a reagent chamber carrier, are produced in a complex process by injection molding and welding in separate processes. The welding process is a challenge because the media-tight composite film is not the same type of plastic as the chamber carrier. For medical products, all components must be biocompatible and germ-free, so that the subsequent analysis results are not falsified become. For this reason, all components of the device are manufactured and packaged under clean room conditions.

Subsequently, the components from the different production areas for assembly in another clean room are merged. By in this procedure 200 presented lesser individual processes and the lower logistics costs can easily significantly fewer sources of error and contamination arise, which can be prevented in known methods only with great time and cost.

3 shows a perspective view of a composite film 105 according to an embodiment. This may be the in 1 described composite film 105 Act, with the difference that the lid area 130 according to this embodiment not yet along the Umklapplinie 133 on the chamber area 125 was worked.

4 shows a cross section of a composite film 105 with a carrier plate 110 according to an embodiment. These may be the ones based on 1 described composite film 105 and the carrier plate 110 Act, with the difference that the lid area 130 the composite foil 105 according to this embodiment not yet along the Umklapplinie 133 on the chamber area 125 the composite foil 105 was worked.

The composite foil 105 is according to this embodiment in an injection mold between a first injection mold 400 and a second injection mold 405 added. One in the second injection mold 405 arranged vacuum device 410 is designed to be the composite film 105 to hold in a form shown here. The chambers 135 are previously, for example, by a deep drawing process and / or a folding process in the chamber area 125 been formed. The first injection mold 400 is shaped to a shape of the carrier plate shown here 110 to allow for injection and curing of a carrier plate material. The lid area 130 is according to this embodiment by a slider 415 fixed the cover area 130 seals against the injecting carrier plate material. A the lid area 130 contacting Teflon insert 420 of the slider 415 is designed to soften at high temperatures of 100 ° C to 140 ° C, around the composite film 105 not to damage. According to this embodiment, the injection mold is formed to a support plate 110 to produce with at least one fluid channel.

If an exemplary embodiment comprises a "and / or" link between a first feature and a second feature, then this is to be read so that the embodiment according to one embodiment, both the first feature and the second feature and according to another embodiment either only first feature or only the second feature.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• DE 102010041287 A1 [0003]

Claims (10)

Procedure ( 200 ) for producing a fluidic device ( 100 ) for a lab-on-chip system, the method ( 200 ) comprises at least the following steps: 205 ) at least one chamber ( 135 ) in a chamber area ( 125 ) of a composite film ( 105 ); - Injection ( 210 ) a chamber bottom outside of the chamber area ( 125 ) with a backing plate material; - Fill ( 215 ) of the at least one chamber ( 135 ) with at least one fluid ( 115 ); - fold down ( 220 ) of a cover area ( 130 ) of the composite film ( 105 ) to the at least one chamber ( 135 ), the lid area ( 130 ) in another area of the composite foil ( 105 ) as the chamber area ( 125 ) is arranged; and - sealing ( 225 ) of the lid area ( 130 ) with the chamber area ( 125 ) in the region of the at least one chamber ( 135 ) to the chamber ( 135 ) fluid-tight seal. Procedure ( 200 ) according to claim 1, wherein in the step of forming ( 205 ) the at least one chamber ( 135 ) in a chamber area ( 125 ) of the composite film ( 105 ), which forms substantially one half of a surface of the composite film ( 105 ). Procedure ( 200 ) according to one of the preceding claims, wherein in the step of forming ( 205 ) a plurality of chambers ( 135 ) in the chamber area ( 125 ) of the composite film ( 105 ) is formed. Procedure ( 200 ) according to one of the preceding claims, wherein in the step of forming ( 205 ) the at least one chamber ( 135 ) is formed by a deep-drawing process and / or a folding process. Procedure ( 200 ) according to one of the preceding claims, wherein in the step of forming ( 205 ) the at least one chamber ( 135 ) in a fluid-tight molded composite film ( 105 ) is formed, in particular wherein the fluid-tight molded composite film ( 105 ) has at least partially an aluminum layer. Procedure ( 200 ) according to one of the preceding claims, wherein in the step of injection molding ( 210 ) the lid area ( 130 ) of the composite film ( 105 ) by a slider ( 415 ) is fixed, the cover area ( 130 ) seals against the injecting backing plate material. Procedure ( 200 ) according to any one of the preceding claims, comprising a step of cooling ( 230 ) in response to the injection step ( 210 ), wherein in the cooling step ( 230 ) a cooling of the carrier plate material is effected. Procedure ( 200 ) according to one of the preceding claims, in which in the step of sealing ( 225 ) the lid area ( 130 ) with the chamber area ( 125 ) by at least one U-shaped sealing seam ( 120 ), in particular wherein the U-shaped sealing seam ( 120 ) of a folding line ( 133 ), along which the lid area ( 130 ) was folded, is arranged opposite. Procedure ( 200 ) according to one of the preceding claims, wherein in the step of injection molding ( 210 ) a carrier plate ( 110 ) is produced and / or injected with at least one fluid channel. Fluidic device ( 100 ) for a lab-on-chip system, wherein the device ( 100 ) comprises at least the following features: a composite foil ( 105 ) with a chamber area ( 125 ) and one on the chamber area ( 125 ) folded lid area ( 130 ), the chamber area ( 125 ) at least one of the lid portion ( 130 ) extending chamber ( 135 ) formed by the lid area ( 130 ) is closed; - a carrier plate ( 110 ) located on a lid ( 130 ) facing away from the chamber bottom outside of the chamber area ( 125 ) is attached by means of an injection molding process; - at least one in the chamber ( 135 ) arranged fluid ( 115 ); and at least one sealed seam ( 120 ), which cover the lid ( 130 ) with the chamber area ( 125 ) in the region of the at least one chamber ( 135 ) sealed in such a way that the chamber ( 135 ) is sealed fluid-tight.

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