EP3393661A1

EP3393661A1 - Microfluidic device, production method, and method for operating a microfluidic device

Info

Publication number: EP3393661A1
Application number: EP16808605.6A
Authority: EP
Inventors: Thomas BRETTSCHNEIDER; Jochen Rupp; Daniel Czurratis; Christian Dorrer; Karsten Seidl
Original assignee: Robert Bosch GmbH
Current assignee: Robert Bosch GmbH
Priority date: 2015-12-22
Filing date: 2016-12-06
Publication date: 2018-10-31
Anticipated expiration: 2036-12-06
Also published as: DE102015226417A1; ES2766528T3; EP3393661B1; US11065621B2; CN108472648B; US20210162403A1; CN108472648A; KR20180093254A; WO2017108387A1

Abstract

The invention relates to a microfluidic device (100). The device (100) comprises a chamber substrate (105) with a fluid chamber (110) for receiving a fluid, a cover substrate (115) with a punch opening (125), said punch opening (125) lying opposite a fluid chamber opening (130) of the fluid chamber (110), a flexible membrane (135) which is arranged between the chamber substrate (105) and the cover substrate (115) and which spans the punch opening (125) and the fluid chamber opening (130), and a punch unit (120) which is designed to be brought into the fluid chamber (110) through the punch opening (125) in order to deflect the membrane (135) into the fluid chamber (110) in order to allow the fluid to flow out of the fluid chamber (110) when the fluid is received in the fluid chamber (110).

Description

description

title

Microfluidic device, method for manufacturing and method for operating a microfluidic device

State of the art

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

In microfluidic devices, liquids are provided or transported on a chip. Such microfluidic devices can be used, for example, in so-called lab-on-a-chip systems (LOCs), in which the entire functionality of a macroscopic laboratory is accommodated on, for example, a credit card-sized plastic substrate (LOC cartridge) and complex biological, diagnostic, chemical or physical processes can be miniaturized. Many LoC systems require a variety of fluids, such as liquid reagents, such as: As saline solutions, ethanol-containing solutions, aqueous solutions, detergents or dry reagents, such as lyophilisates, salts, etc., which are required for a variety of diagnostic applications. These reagents can either be manually pipetted onto the LOC cartridge or pre-stored on the cartridge. The latter brings advantages in terms of automation, contamination risks, user-friendliness and transportability of LOC systems.

WO 2014/090610 Al describes a concept in which liquids are stored in tubular bags, so-called stickpacks. The stickpacks are integrated into the LOC system, where they can be opened and emptied via a deflection of a flexible membrane. Disclosure of the invention

Against this background, with the approach presented here, a microfluidic device and a method for manufacturing and a

Method for operating a microfluidic device according to

Main claims presented. The measures listed in the dependent claims advantageous refinements and improvements of the independent claim microfluidic device are possible.

An advantage of the described microfluidic device is that liquids, such as reagents and moisture-sensitive dry reagents for LOC applications stored for a long time stable and if necessary on a

mechanical element, such as a stamp, a stamp unit, or a plunger can be provided.

There is provided a microfluidic device comprising: a chamber substrate having a fluid chamber for receiving a fluid; a lid substrate having a punch opening, the punch opening being disposed opposite to a fluid chamber opening of the fluid chamber; a flexible membrane sandwiched between the chamber substrate and the

Cover substrate is arranged and the punch opening and the

Spans fluid chamber opening; and a punch unit configured to retract into the fluid chamber through the punch opening to deflect the membrane into the fluid chamber to allow the fluid to flow out of the fluid chamber when the fluid is received in the fluid chamber.

The chamber and lid substrate may be a polymeric substrate of high barrier plastics. The Membrane is designed to be deflected at a pressure on the membrane. The membrane is highly flexible and tear-resistant in one embodiment. In one embodiment, the membrane is configured to retract to its original position upon a withdrawal of the pressure. Especially with a large deflection of the

Membrane can also lead to a plastic deformation, which is not necessarily the function in the way.

An imagined mechanical stamping unit of the microfluidic device enables reliable reagent release. Since a high force can be safely applied to the example containing a fluid fluid chamber, the fluid can, for example, in a blister or behind a

Barrier film are stored with a particularly strong layer structure, which allows safe and long-term stable storage of the fluid. The presented membrane has the advantage that the stamp unit can always remain separated from the fluid and thus due to the hygienic

Application is reusable. This can create a cost advantage. The fluid chamber may, for example, have a volume less than 30 ml, 20 ml, 10 ml, 5 ml, 1 ml or less than 0.1 ml. In addition, a mechanically movable punch unit has the advantage that the release of the reagents does not necessarily have to be gravity-driven. The stamp unit can displace the volume of reagent through the membrane into other chambers or channels, wherein the entire structure can be arbitrarily aligned, for example at 0 ° inclination, but also under, for example, 30 °, 45 ° or 60 ° tilt. This offers advantages in handling and processing of the LOC cartridge.

The fluid may be received in the fluid chamber and held in the fluid chamber by a barrier film closing the fluid chamber. In this case, the barrier film may be formed to be opened by the stamp unit, for example, a channel or a

Fluidic transfer chamber to connect with the fluid chamber. By means of such a barrier film, the fluid, such as a reagent, can be stored safely in the fluid chamber and can be released selectively only when required by introducing the stamp unit into the barrier film. According to one embodiment, the fluid can be arranged in an insertion container, which is received by the fluid chamber, wherein the

Barrier foil closes the insert container. Such a depositor has the advantage that a direct filling of the fluid chamber can be avoided and thus simplifies manufacturing, simplifies use and incorrect operation and the risk of contamination can be excluded. According to various embodiments, the insert container may be flexible or plastically shaped.

The insert may be formed so that it can be accommodated accurately in the fluid chamber, the material of the insert can thereby a higher

Have barrier property with respect to the fluid as the chamber substrate. Thus, different fluids with different requirements for a long-term stable Vorlagerung in specially designed for the requirements of the fluids depositors are stored safely in the device. A choice of material of the chamber substrate can thus be carried out independently of suitable for fluids storage materials. The fluid may also be arranged in a blister which is received by the fluid chamber, wherein the blister is a volume of the fluid chamber in the

Substantially, wherein the blister is formed to be opened by the stamp unit. For example, a blister can be formed from one or more sealing films whose edges can be connected by tight sealing seams and a cost-effective alternative for one

Depict depositor. A blister of an elastic material can

For example, simply taken in fluid chambers with different shapes, for example, glued be. It is advantageous if a diameter of the punch opening according to a

Embodiment is greater than half the diameter of the

Fluid chamber opening. The diameter of the punch opening can

advantageously have a diameter corresponding to the diameter of the fluid chamber opening. Thus, the volume of the fluid chamber can almost completely displace. A stamp tip of the stamp unit can advantageously be formed so that the fluid is displaced in the fluid chamber in the direction of a channel.

The stamp unit can in further advantageous embodiments

Assume geometries on the face, which promote cracking of the barrier film in the direction of the rearrangement chamber without damaging the flexible membrane. Particularly advantageous are stamp geometries, the

Have elevations on the front side of the stamp unit in order to promote by local stress peaks the onset of cracking of the barrier film exactly in this area. Upon further immersion of the stamp unit, the cracking continues and the displacement of the reagents gets a corresponding preferred direction. This allows a controlled displacement of the reagents in the rearrangement chamber.

A simple method is to stamp the stamp with a defined one

Feed rate (typically 1 mm / min to 50 mm / min) procedure until the end face of the punch unit abuts the bottom of the fluid chamber. Furthermore, it proves to be advantageous to make the process of the stamp step-shaped. The stamp unit moves in the first step until the first tear of the barrier film. In the second step, the stamp unit retracts a few millimeters to allow the reagent to escape through the resulting cracks. In the third step, the stamp unit moves to the bottom of the fluid chamber for a complete displacement of the liquid in the

Rearrangement chamber. Here are any further variations of the

Feed rate and the sequence of the travel direction of the

Stamp unit conceivable to allow optimal and efficient reagents release in the rearrangement chamber.

The device may have a channel which extends on a chamber substrate side facing the membrane and is fluidly connected to the fluid chamber. The channel can open into the fluid chamber. At one of the fluid chamber opposite end of the channel, a

Rearrangement chamber be arranged for safe collection of the fluid. In the rearrangement chamber, for example, another fluid may be upstream, for mixing with the fluid after the release of the fluid can be determined. Alternatively, such a rearrangement chamber can also open directly into the fluid chamber.

The diameter of the punch opening may be smaller than half the diameter of the fluid chamber opening. In this case, the punch opening may be arranged adjacent to the channel. A relatively small one

Stamp opening can accommodate a correspondingly small stamp unit, which in turn can make room for example, a further punch opening and / or for a vent on the side of the fluid chamber opening available. Advantageously, the channel can be arranged at a certain angle of inclination of the device so that the fluid can flow off or be sucked off in a gravity-directed direction. When the die opening is arranged as shown adjacent to the channel, the vent opening can be arranged, for example, over the die opening, from where

For example, an inflow of ambient air through the vent opening can promote the outflow of the fluid.

The channel may have a channel extension and the lid substrate a

Having vent opening, which opens into the channel extension, wherein the punch opening can be arranged between the vent opening and the channel, wherein the membrane does not span the vent opening.

An imaginary vent opening above the channel with connection to the channel can favor, for example, due to an established connection to the ambient air, a drainage of the fluid through the channel.

The lid substrate may have a vent opening which fits into the

Fluid chamber opens, the punch opening between the

Vent and the channel can be arranged, wherein the membrane can span the vent. The apparatus may further comprise a further punch unit adapted to retract into the fluid chamber through the vent opening to deflect the diaphragm into the fluid chamber to allow inflow of further fluid into the fluid chamber. A proposed approach allows the opening of a fluid chamber sealed by the barrier film, for example, and / or the opening of a blister disposed in the fluid chamber at two different locations. The approach is also the basic requirement for a possibly additional air duct with connection to the vent and the

Fluid chamber, which can allow an inflow of another fluid into the fluid chamber.

It is advantageous if, according to one embodiment, between the

Chamber substrate and the membrane, an intermediate substrate is arranged, which has a die opening continuing further punch opening and a vent opening continuing further vent opening and is formed to produce a transverse to the vent opening and opening into the further vent opening air duct.

The air duct may extend in a direction facing away from the channel. An imaginary air duct can create a negative pressure in the

Balance the fluid chamber after the stamping operation and during the outflow of the fluid by an inflow of, for example, ambient air through the air passage into the fluid chamber and thus promote the outflow of the fluid through the channel. In addition, the intermediate substrate prevents an air path for venting during active intake of the released fluid. Otherwise there is a risk that only air is sucked in instead of liquid. The channel can run between the membrane and the intermediate substrate and open into the punch opening. This approach allows a favorable arrangement of the channel when an intermediate substrate is placed in the device. A diameter of the fluid chamber opening may be the punch opening

correspond, wherein the fluid chamber may have a second punch opening which corresponds to a diameter of the further vent opening.

The chamber substrate can be so except in the field of

Fluidkammeröffnung and in the region of the second fluid chamber opening via a Fluidkammeröffnungsseite at the fluid chamber opening and the second Fluid chamber opening are arranged extend. The chamber substrate can be formed more stable. A possibly arranged barrier film for closing the fluid chamber may, according to this embodiment, for example be glued along an inside of the fluid chamber facing the fluid chamber opening side and / or arranged between the chamber substrate and the intermediate substrate. If the barrier film between the

Chamber substrate and the intermediate substrate is arranged, the

Barrier film, the fluid chamber opening and the second fluid chamber opening and the further vent opening and the further punch opening of the

Span over the intermediate substrate.

A fluid chamber bottom opposite the fluid chamber opening may be formed by a further barrier film. Due to the above-described increased stability of the chamber substrate on the fluid chamber opening side, the opposite fluid chamber bottom of the chamber substrate can only be formed by the further barrier film. The chamber substrate may for example be previously filled by the side of the fluid chamber floor and

then be closed by the further barrier film. In addition, during the stamping process by the at least slightly more flexible further barrier film resulting from the retraction of the stamp units internal pressure in the fluid chamber by a slight movement of the other

Barrier film in the direction of the punch movement, be balanced. In this further advantageous embodiment with additional barrier film, the formation of an air path during active suction of the fluid is completely excluded, since the bottom of the fluidic chamber over the entire surface with the

Intermediate substrate is connected.

A method for manufacturing a microfluidic device comprises the following steps:

Providing a chamber substrate having a fluid chamber for receiving a fluid,

Providing a lid substrate with one opposite to a

Fluid chamber opening of the fluid chamber arranged punch opening; Disposing a flexible membrane between the chamber substrate and the lid substrate, the membrane spanning the die opening and the fluid chamber;

Optionally, creating a channel on a side of the membrane facing the chamber substrate, the channel being fluidly connected to the fluid chamber; and providing a stamp unit adapted to pass through

Retracting the die opening into the fluid chamber to deflect the diaphragm into the fluid chamber to allow outflow of the fluid from the fluid chamber when the fluid is received in the fluid chamber.

A method of operating a said microfluidic device comprises the following step:

Retracting the stamper unit through the stamper opening into the fluid chamber to deflect the diaphragm into the fluid chamber to allow outflow of the fluid from the fluid chamber when the fluid is received in the fluid chamber.

Embodiments of the invention are illustrated in the drawings and explained in more detail in the following description. It shows:

1 is a schematic cross-sectional view of a microfluidic device according to an embodiment;

FIG. 2 is a cross-sectional view of a microfluidic device according to an embodiment; FIG.

3 is a cross-sectional view of a microfluidic device according to an embodiment; 4 is a cross-sectional view of a microfluidic device according to an embodiment;

5 is a cross-sectional view of a microfluidic device with insertion container according to an embodiment;

6 is a perspective view of a chamber substrate having a plurality of fluid chambers according to an embodiment;

7 is a cross-sectional view of a microfluidic device with a vent opening according to one embodiment;

8 is a cross-sectional view of a microfluidic device with a vent opening according to one embodiment;

9 is a cross-sectional view of a microfluidic device with an intermediate substrate and a further stamping device according to a

Embodiment;

10 is a cross-sectional view of a microfluidic device with an intermediate substrate and a further stamping device according to a

Embodiment;

11 is a cross-sectional view of a microfluidic device with a further barrier film according to an exemplary embodiment;

12 is a cross-sectional view of a microfluidic device with a further barrier film according to an embodiment;

13 is a cross-sectional view of a microfluidic device with a further barrier film according to an exemplary embodiment;

14 shows a cross-sectional view of a microfluidic device with a further barrier film according to an exemplary embodiment; 15 is a perspective view of a device having a plurality of fluid chambers according to an embodiment;

16 is a flowchart of a method of manufacturing a

microfluidic device according to an embodiment; and

17 is a flowchart of a method for operating a

Microfluidic device according to one embodiment. In the following description of favorable embodiments of the present invention are for the in the various figures

represented and similar elements acting the same or similar

Reference numeral used, wherein a repeated description of these elements is omitted.

FIG. 1 shows a schematic cross section of a microfluidic device 100 according to one exemplary embodiment. The device 100 comprises a chamber substrate 105 with a fluid chamber 110 and a cover substrate 115 arranged adjacent to the chamber substrate 105. The cover substrate 115 is disposed between the chamber substrate 105 and a stamp unit 120

arranged. The lid substrate 115 has a punch opening 125 and the fluid chamber 110 has a fluid chamber opening 130. Between the

Chamber substrate 105 and the cover substrate 115, a flexible membrane 135 is arranged, which spans the fluid chamber opening 130 and the adjacent arranged punch opening 125. On a chamber substrate 105

facing side of the membrane 135 optionally extends a channel 140 which is fluidly connected to the fluid chamber 110.

In a variant, the channel 140 extends on a side of the cover substrate 115 facing the membrane 135. The channel is then penetrated via a through hole in the cover

Membrane 135 fluidly connected to the fluid chamber 110. The diameter of the punch opening 125 in this variant is advantageously smaller than the diameter of the fluid chamber opening 130, so that the channel 140 in the

Cover substrate 115 to one of the fluid chamber opening 130th

can be performed opposite position. The stamp unit 120 is shaped to retract into the fluid chamber 110 through the lid substrate 115. The stamp unit 120 according to this exemplary embodiment has, on a side facing the cover substrate 115, a rounded stamp tip which corresponds to an internal geometry of the fluid chamber 110. As the stamp unit 120 retracts into the fluid chamber, the diaphragm 135 is deflected from the rounded punch tip of the stamp unit 120 into the fluid chamber 110. When the stamp unit 120 is made of the

Fluid chamber moves back, takes the diaphragm 135 according to a

Embodiment, its original position, which is shown in Fig. 1, a again. Alternatively, the membrane 135 remains at least partially deformed after retraction of the stamp unit 120.

For example, a fluid may be contained in a blister in the fluid chamber 110. The fluid may also be filled directly into the fluid chamber, wherein the fluid chamber opening 130 may then be closed by a barrier film, so that the fluid can not flow into the channel 140. The fluid may alternatively be accommodated in an insert container accommodated in the fluid chamber 110, wherein the insert container may be closed by the barrier film.

By way of example, the microfluidic device 100 is shown in FIG. 1 in a position with a 0 ° inclination.

FIG. 2 shows a schematic cross section of a microfluidic device 100 according to one exemplary embodiment. This may be the microfluidic device 100 described with reference to FIG. 1, with which

Difference that the fluid chamber in Fig. 2, the barrier film 200 and disposed in the fluid chamber 110 fluid 205 has. Furthermore, the

Device 100 has a transfer chamber 210 with a valve 215.

The fluid 205 is received directly in the fluid chamber 110 according to this embodiment, the barrier film 200 closing the fluid chamber opening, whereby the fluid 205 is securely held in the fluid chamber 110. According to this embodiment, the fluid 205 does not completely fill the fluid chamber 110, it may be another content such as gas or air in the fluid chamber 110 may be arranged. The fluid 205, according to an alternative embodiment, may also be received in a blister disposed in the fluid chamber 110. The rearrangement chamber 210 is according to this embodiment with the

Channel 140 is connected, wherein the channel 140 between the fluid chamber 110 and the rearrangement chamber 210 is arranged. The rearrangement chamber 210 is arranged below the fluid chamber 205 according to this embodiment. The rearrangement chamber 210 has the valve 215 on a side facing away from the fluid chamber 110.

The details already described are explained in more detail below with reference to FIG. 2: The LOC system 100 in the form of the microfluidic device 100 can consist of polymer-based multilayer structures in the form of the chamber substrate 105 and the cover substrate 115. The chamber substrate 105 and the

Cover substrate 115 comprise polymer-based substrates in which cavities in the form of fluid chamber 205 and / or channel 140 are arranged. A storage of liquids 205, hereinafter referred to as fluids 205, with small volumes below 1 ml is only conditionally possible in the fluid chamber 110 of the chamber substrate 105, since most plastics do not have sufficient barrier properties for long-term stable storage (PC, PA, US Pat. PS, PMMA). In addition, it is important that the fluid 205, such as a reagent, in the initial state is closed, z. B. by normally-closed

Valves 215, and when needed (on-demand) can be provided, which implies additional requirements for storage concepts. Therefore, in order to store the fluid 205 in a stable manner, according to this embodiment, a separate container, such as a blister pack or a tubular bag in the form of the blister, can be accommodated in the fluid chamber 110, whereby the

Chamber substrate 105 is not limited in its choice of materials. This implies requirements on the manufacturing process due to handling and pick-and-place processes. Advantageously, the chamber substrate 105 is made of plastics having high barrier properties, such as COP, COC, PP, PE or PET, allowing for safe fluid or reagent pre-storage in the chamber substrate 105 allows. A concept based on such plastics can be integrated directly into the material system of the fluid chamber 110 or through a joining process

For example, bonding, welding, or clamping fluidly connected to the fluid chamber 110.

The device 100 shown has, according to one exemplary embodiment, a polymer layer structure consisting of at least two polymer substrates, namely the chamber substrate 105 and the cover substrate 115, which are separated by the flexible membrane 135. In the chamber substrate 105, an upstream fluid 205 is arranged, for example in the blister, in a sealed injection-molded insert container or in an opening in the form of the one which is closed by the or more barrier films 200

Fluid chamber 110 within the chamber substrate 105. To provide the upstream fluid 205 at least one punch unit 120, for example a plunger is used, which can penetrate through at least one opening in the form of the punch opening 125 in the lid substrate 115 by relative movement in the LOC in the form of the fluid chamber 110 , 3 shows a schematic cross section of a microfluidic device

100 according to an embodiment. This can be the device 100 described with reference to FIG. 2, with the difference that, according to this exemplary embodiment, the stamp unit 120 is inserted into the stamp opening and the barrier film 200 is opened by the stamp unit 120.

Here, the flexible membrane 135 is deflected by the stamp unit 120 without tearing. Upon contact with the barrier film 200 is caused by the

Stamp unit 120 exerted a force, which leads to the tearing of a sealing foil of the arranged for example in the fluid chamber 110 blister and / or the barrier film 135.

4 shows a schematic cross section of a microfluidic device 100 according to one exemplary embodiment. This may be the device 100 described with reference to FIG. 3, with the difference that according to this embodiment, the stamp unit 120 is completely in the Fluid chamber 110 is inserted and the fluid 205 is displaced into the rearrangement chamber 210.

The fluid 205 is either in a supply chamber 210, previously referred to as rearrangement chamber 210, displaced or

emptied into the connected microfluidic channel 140 after retraction of the stamp unit 120.

The result of the described approach is the advantage of a reliable provision of the fluid 205 by the mechanically actuated punch unit 120 or the plunger. Moreover, on the introduction of defined

Predetermined breaking points in, for example, the barrier film by z. As laser ablation be dispensed with, as can be exercised by the stamp unit 120 safely very large forces on the barrier film or the sealing film. It eliminates an associated additional manufacturing step. By using the mechanically actuated stamping unit 120, for example barrier films can be used, which have a strong layer structure and / or are formed very thick, for. B. by PP and metal layers, in particular

Aluminum, these can still be broken up reliably. This also favors the long-term stable storage of the fluid 205.

The stamping unit 120 advantageously does not come into contact with the upstream fluid 205 during the entire release process. The flexible membrane 135 enables complete separation from the mechanical actuation mechanism in the form of the stamp unit 120 and the fluid 125 in the fluid chamber 110 a

Actuator be installed and need not together with the example used blister or insert in the form of

Disposal container be disposed of. As a result, both the costs for the device 100 and the costs for a drive unit remain low, since this requires no additional mechanism in order to grip a punch unit 120 accommodated on the device 100.

According to this embodiment, this is based

Reagent storage concept on the chamber substrate 105 from a polymeric substrate with integrated fluid chamber 110, which through the

Barrier film is sealed. The chamber substrate 105 may be made of plastics having high barrier properties, e.g. B. PP,

PE, COC, COP, or have additional coatings such as Al, AI203, SiO, the requirements for long-term storage of fluids such as 205

Liquid reagents meet. The chamber substrate 105 is connected to the flexible

Membrane 135 and another polymeric substrate, the cover substrate 115, connected. As joining processes for this multi-layer structure are

Laser transmission welding, ultrasonic welding, thermal bonding, gluing, clamping or similar processes suitable. The cover substrate 135 has at least one opening in the form of the punch opening 125. For the release of the fluid 205, the stamp unit 120 moves through the

Stamp opening 125, deflects the flexible membrane 135 without this breaks, and breaks up the barrier film. In this case, the fluid 205 is displaced via the transfer channel in the form of the channel 140 into the rearrangement chamber 210 and is ready for further microfluidic processes. For example, the fluid 205 may be sucked when opening the valve 215 by a negative pressure in a behind it located microfluidic network. The flexible membrane 135 allows a complete fluidic separation between the fluidics in the

Chamber substrate 105 with all participating fluids 205 and the mechanical

Stamp unit 120. The stamp unit 120 is preferably formed so that it displaces as large a volume as possible from the fluid chamber 110, without sealing at the edges of the fluid chamber 110 so that the fluid 205 no longer enters the rearrangement chamber 210. This is best achieved if the shape of the stamp unit 120 is the inverse of the

Fluid chamber 110 corresponds to, but for example, a few hundred

μηη tolerance on the outer walls has.

For punch unit 120, according to an alternative exemplary embodiment, any desired geometries, dimensions and shapes are conceivable

Rupture of the barrier film and / or the sealing film and a directed emptying of the fluid chamber 110 favor. For example, the stamp unit 120 can hold a recess directed to the rearrangement chamber 210 in order to promote the displacement of the fluid 205 into the rearrangement chamber 210. It can thus be minimized crosstalk of the fluid 205. FIG. 5 shows a schematic cross section of a microfluidic device 100 with insertion container 500 according to one exemplary embodiment. This may be the device 100 described with reference to FIG. 2, with the difference that, according to this exemplary embodiment, the insert container 500 having a cavity 505 is received by the fluid chamber 110. The fluid 205 is disposed in the cavity 505 of the loading container 500. The fluid chamber 110 according to this embodiment has a rectangular shaped cross-section to accommodate the insertion tray 500, which also has a rectangular cross-section according to this embodiment. The insert container 500 can be inserted with a precise fit or approximately exact fit into the fluid chamber 110. Due to the separate insert container, the channel 140 or the wall between the fluid chamber 110 and the rearrangement chamber 210 can be completely eliminated in an advantageous and space-saving embodiment. According to one embodiment, the fluid chamber 110 and the rearrangement chamber 210 are combined into one chamber, or in other words, the rearrangement chamber 210 and the inserter bin 500, also referred to as an inserter, are not separated. Alternatively, the wall between the fluid chamber 110 and the rearrangement chamber 210 may be reduced to a small indentation, as a ridge for holding the insert container 500 in the fluid chamber 110, or forming the channel 140

Having passage opening.

In this further advantageous embodiment, the additional

Insert container 500 integrated into the chamber substrate 105. The insert container 500 ideally has higher barrier properties than the surrounding chamber substrate 105. This insert container 500 contains the fluid 205 and is sealed to the barrier film 200. The release of the fluid 205 is identical, as described in the preceding figures. The material selection of the chamber substrate 105 remains independent of the requirements of the long-term stable reagent pre-storage according to this embodiment.

The insert container 500 can be glued, clamped, welded or integrated by other joining methods. The loading container 500 may also be easily inserted into a suitably shaped receiving chamber in the form of the fluid chamber 110 in the Chamber substrate 105 has been inserted. By properly formed, it is meant here that the fluid chamber 110 closely encloses the loading container 500. This has the advantage that the dead volume of the structure is minimized and slipping of the loading container 500 is avoided.

The loading container 500 has according to this embodiment, the cavity 505 for receiving the fluid 205, but according to an alternative embodiment, also have a plurality of such cavities 505, the z. B. each filled with different fluids 205. These cavities 505 may be arranged in the form of a bar or only in certain places, for. B. at the top, comb-like with each other. This has the advantage that in the fluid chamber 110 separating elements, for. As walls, may be arranged between the various fluids 205, which can reliably prevent mixing of the fluids 205. Furthermore, the deflection of the flexible membrane 135 by the movable plunger unit causes the fluidic path to be sealed at the connection recesses 605 shown in FIG. 6 in order to be able to reliably prevent mixing of the fluids 205 stored in separate fluid chambers 110 after their release.

6 shows a perspective view of a chamber substrate 105 with a plurality of fluid chambers 110 according to one exemplary embodiment. This may be the chamber substrate 105 described with reference to FIG. 5, with the difference that no fluid in the cavities 505 of FIG

Shelf 500 is included. According to this exemplary embodiment, the chamber substrate 105 has four fluid chambers 110 arranged next to one another. The number of fluid chambers 110 is merely exemplary, so that more or fewer than four fluid chambers 110 may be provided. Below the fluid chambers 110 four rearrangement chambers 210 are arranged according to this embodiment. The fluid chambers 110 according to this embodiment, the insertion container 500, wherein the

Insert container 500 is formed according to this embodiment as a four cavities 505 comprehensive insert container 500, wherein one of the cavities 505 is received in each case in one of the four fluid chambers 110. According to this embodiment, the insertion tray 500 in a

Rearrangement chambers 210 remote area between the cavities 505th three connecting webs 600 on. The chamber substrate 105 has in the region corresponding to the connecting webs 600 three connecting recesses 605 for receiving the connecting webs 600. 7 shows a cross section of a microfluidic device 100 with a

Vent opening 700 according to one embodiment. This may be the device 100 described with reference to FIG. 3, with the difference that the punch opening 125 is smaller than in FIG. 3 and arranged in the region of the channel 140, and that the channel 140 has a

Channel extension 705 having the vent opening 700.

The channel extension 705 extends according to this embodiment in a direction away from the channel 140, the punch opening 125 is arranged between the channel extension 705 and the channel 140. Of the

Channel extension 705 is also disposed between the fluid chamber 110 and the diaphragm 135. The channel extension 705 extends according to this

Embodiment over a height 710 of the fluid chamber 110, wherein the vent opening 700 transversely to the channel extension 705 opens into an out of the height 710 disposed end of the channel extension 705. The vent opening 700 extends on a side facing away from the stamp opening 100 side

Fluid chamber 110 according to this embodiment in parallel to the

Stamp opening 125.

According to this exemplary embodiment, a blister is embedded in the chamber substrate 105 in such a way that two sealed sealing areas 715 of the blister rest on a surface provided in the chamber substrate 105 and can be glued there, for example. The lid substrate 115 has the vent opening 700, under which the membrane 135 is opened on.

The punch opening 125 is closed by the membrane 135. The

Stamp unit 120 may enter the assembly through die opening 125

Penetrate the shape of the device 100 and pierce the barrier film 200 and the sealing foil surrounding the blister. The fluid 205 may then be discharged through the channel 140. This exemplary embodiment has the particular advantage that it is possible to dispense with an additional provision chamber in the form of the rearrangement chamber. Thus, this allows Embodiment, a particularly space-saving possibility for Vorlagerung the fluid 205th

8 shows a cross-section of a microfluidic device 100 with a vent opening 700 according to one exemplary embodiment. This can be the device 100 described with reference to FIG. 7, with the difference that the stamp unit 120 according to this exemplary embodiment is led out of the device 100 again, as a result of which the diaphragm 135 in the region of the stamp opening 125 is retracted and the fluid 205 flows into the channel 140.

9 shows a cross-section of a microfluidic device 100 with an intermediate substrate 900 and a further stamp unit 905 according to one exemplary embodiment. This may be the device 100 described with reference to FIG. 7, with the difference that the channel 140 has no channel extension and the vent opening 700 is arranged in a region of the height 710. The intermediate substrate 900 is between the

Chamber substrate 105 and the lid substrate 115 arranged. The

Intermediate substrate 900 has a further vent opening 910 and a further punch opening 915.

The further punch opening 915 continues the punch opening 125 and the further vent opening 910 continues the vent opening 700. The intermediate substrate 900 is formed to be one in the other

Venting channel 910 opening air duct 920 to form. The air channel 920 is arranged transversely to the further venting channel 910 on a side of the membrane 135 facing the fluid chamber 110. The air duct 920 extends in a direction away from the punch opening 125. The others

Stamp unit 905 is according to this embodiment by the

Vent 700 and the further vent 910 in the

Fluid chamber 110 introduced. The further stamping device 905 opens according to this embodiment, the barrier film 200 and / or the sealing film of the example recorded blister in a region in which the fluid 205 is not arranged in the position shown in Fig. 9. According to this Embodiment, the two sealing areas 715 between the

Chamber substrate 105 and the intermediate substrate 900 arranged.

According to this embodiment, a second plunger in the form of the further stamp unit 905 is used to push a second opening into the barrier film 200 and / or the sealing film of a blister. Since blisters are not completely filled due to their production, it is particularly advantageous to make the second opening at a location of the stickpack, ie the blister, behind which there is air or gas. This embodiment has the particular advantage that the blister can be ventilated via the air duct 920 and thus a particularly high emptying efficiency is achieved.

In an alternative embodiment, the fluid 205 is directly in the

Fluid chamber 110 upstream, which is sealed by the barrier film 200. The arrangement is chosen so that the barrier film 200 in the

Sealing areas 715 is connected flat with the chamber substrate 105. to

Fluid release, the two mechanical punch units 120, 905 in the anticipated breakthroughs in the form of the punch opening 125 and the

Vent 700 in the lid substrate 115 and the other

Stamp opening 915 and the other vent 910 im

Intermediate substrate 900 process and deflect the flexible membrane 135 from. In this case, the barrier film 200 is broken open in the region of the additional punch opening 915 and the further vent opening 910. Will the

Stamping devices 120, 905 moved back, are the

Venting path in the form of the air channel 920 and the fluidic path in the form of the channel 140 released.

An example polymeric sealing layer of the barrier film 200 has

in particular the advantage that the mechanical deformation after the

Retracting the mechanical punch devices 120, 905 is maintained, which is the blockade-free opening of the channel 140 and the pneumatic

Air duct 920 ensures. It is also particularly advantageous to design the further stamping unit 905 so that it penetrates the barrier film 200 in front of the stamping unit 120. In this way, it is ensured that any overpressure occurring within the fluid chamber 110 can escape before the stamp unit 120 penetrates. With different execution The stamp units 120, 905 can continue to be a simultaneous actuation.

10 shows a cross-section of a microfluidic device 100 with an intermediate substrate 900 and a further stamp unit 905 according to one

Embodiment. This may be the device 100 described with reference to FIG. 9, with the difference that the stamping device 120 and the further stamping device 905 according to this embodiment are led out of the device 100 again, whereby the membrane 135 in the region of the stamp opening 125 and is withdrawn in the region of the vent opening 700, whereby the fluid 205 flows into the channel 140 and another fluid flows from the environment of the device 100 through the air channel 920 into the fluid chamber 110. This embodiment has the particular advantage that after tearing the barrier film and retracting the

Stamping units, the reagent can be actively sucked through the channel 140, at the same time the risk of the formation of an air path up to the vent 700 (as in FIG 7 and FIG 8) is reduced to a minimum. The emergence of an air path for venting 700 would in the worst case, an active suction of the released reagent is no longer possible.

11 shows a cross-section of a microfluidic device 100 with a further barrier foil 1100 according to one exemplary embodiment. This may be the device 100 described with reference to FIG. 9, with the difference that the fluid chamber bottom is formed by the further barrier foil 1100, and that the fluid chamber 110 has a second punch opening 1105. The fluid chamber opening 130 according to this embodiment has a diameter corresponding to the die opening 125. The

Fluid chamber opening 130 is arranged on a side of fluid chamber 110 facing channel 140. The second fluid chamber opening 1105 has a diameter corresponding to the vent opening 700. The second

Fluid chamber opening 1105 is fluidly connected to the further vent opening 910. According to this embodiment, the fluid chamber 110 has a rectangular cross section. The chamber substrate 105 according to this embodiment extends over the punch opening side including the fluid chamber opening 130 and the second punch opening 1105. The Barrier film 200 is according to this embodiment between the

Chamber substrate 105 and the intermediate substrate 900, wherein the barrier film 200 spans the fluid chamber opening 130 and the second punch opening 1105. The barrier film 200 according to this exemplary embodiment is in the region of the fluid chamber opening 130 and in the region of the second one

Fluid chamber opening 1105 through the stamp unit 120 and the other

Stamp unit 905 opened.

In the following, details already explained are described in more detail with reference to FIG. 11:

According to this embodiment, the chamber substrate 105 is sealed on both sides with the barrier films 200, 1100. The sealed on both sides

Chamber substrate 105 with integrated fluid 205 is attached via a joining step, for example by gluing and / or welding and / or clamping on the multi-layer structure of the device 100 that the punch opening 125 and the vent opening 700 on an axis with the openings in the form of the fluid chamber opening 130th and the second fluid chamber opening 1105. This has the particular advantage that in fluid release the

Mechanical stamp units 120, 905 the barrier film 200 defined break open, with no air path between the channel 140 and the

Can form air duct 920, since the chamber substrate 105 is airtight in the remaining area via a planar joining surface 1100 connected to the intermediate substrate 900.

For the release of the fluid 205, the mechanical stamp devices 120, 905 can be moved back and the fluid 205 ready to be actively attracted, for example, in the fluidic channel 140. This results in the advantage that the further barrier film 200 limits the pressure increase within the fluid chamber 110 when the stamp devices 120, 905 are pressed in by a slight bulging. This reduces the risk of leakage when opening.

FIG. 12 shows a cross-section of a microfluidic device 100 with the further barrier foil 1100 according to one exemplary embodiment. This may be the device 100 described with reference to FIG. 11, with which Difference in that the stamping device 120 and the further stamping device 905 are again led out of the device 100 according to this embodiment, whereby the diaphragm 135 in the region of the punch opening 125 and in the region of the vent opening 700 is retracted, whereby the fluid 205 flows into the channel 140 and the further fluid from the environment of the device 100 flows through the air channel 920 into the fluid chamber 110.

FIG. 13 shows a cross section of a microfluidic device 100 with the further barrier foil 1100 according to one exemplary embodiment. This may be the device 100 described with reference to FIG. 11, with the difference that the barrier film 200 according to this exemplary embodiment is arranged on an inner side of the fluid chamber 110 such that it spans the fluid chamber opening 130 and the second fluid chamber opening 1105. The barrier film 200 is according to this embodiment by the

Stamp unit 120 and the other stamp unit 905 opened.

According to this exemplary embodiment, the barrier film 200 is sealed on the inside of the fluid chamber 110, so that no air path between the channel 140 and the air channel 920 can form here as well. The chamber substrate 105 is directly connected to the multi-layer structure of the device 100, that is the

Intermediate substrate 900 via the joining surface 1110 positively or non-positively connected, z. B. by gluing and / or welding and / or terminals. The barrier film 200 may according to an alternative embodiment in the

Chamber substrate 105 in the region of the fluid chamber opening 130 and the second fluid chamber opening 1105 be sunk locally.

The required polymer substrates, ie the starting material, and the required structures in the polymer substrates can be produced for example by milling, injection molding, hot stamping, deep drawing and / or laser structuring.

Material examples for the individual components follow

Devices 100 described above. Materials for the chamber substrate 105 and the lid substrate 115 may be thermoplastics, e.g. PC, PA, PS, PP, PE, PMMA, COP, COC.

Materials for the tray 500 may be thermoplastics, for. PC, PA, PS, PP, PE, PMMA, COP, COC and / or glass.

Materials for the stamping device 120 and the further stamping device 905 may include thermoplastics, for. PC, PA, PS, PP, PE, PMMA, COP, COC, and / or metals such as steel or brass, as well as elastomers.

Coatings of reservoirs, such as fluid chamber 110, may be made with Al, Al 2 O 3, SiO 2.

Materials for membrane 135 may be elastomer, thermoplastic elastomer (TPU, TPS), thermoplastics, or heat sealable films.

As a barrier film 200 and sealing film can be commercially available

Polymer composite films are used from polymeric sealing and protective layers, for. As PE, PP, PA, PET and as a barrier layer, as a rule

evaporated aluminum, but also other high barrier layers such as EVOH,

BOPP.

Exemplary dimensions of elements of the exemplary embodiments follow: The thickness of the chamber substrate 105 and the cover substrate 115 can be from 0.5 to

5 mm. The thickness of the membrane 135 may be 5 to 300 μηη. In a multilayer structure of the barrier films 200, a thickness of the

Barrier layer (i.d. R. Alu) 5 μηη to 500 μηη, a thickness of the polymer layer 5 μηη to 500 μηη, a thickness of the protective layer 5 μηη to 500 μηη and an elastic layer on the sealing film 50 μηη amount to 2 mm.

The volume of the blister can be 100 to 10000 μΙ. Cuboid shapes, cylindrical shapes, cubic shapes and any other suitable shapes and geometries are suitable as forms for the stamp devices 120, 905. FIG. 14 shows a cross section of a microfluidic device 100 with the further barrier foil 1100 according to one exemplary embodiment. This may be the device 100 described with reference to FIG. 12, with the difference that the barrier film 200 according to this exemplary embodiment is arranged on the inside of the fluid chamber 110.

FIG. 15 shows a perspective view of a device 100 with a plurality of fluid chambers 110 according to one exemplary embodiment. This may be one of the devices 100 described with reference to FIGS. 11 to 14. According to this exemplary embodiment, the chamber substrate 105 has four fluid chambers 110 arranged adjacent to one another.

16 shows a flowchart of a method 1600 for producing a microfluidic device according to an exemplary embodiment. This may be one of the devices described with reference to FIGS. 1 to 5.

In a step of providing 1605, a chamber substrate having a fluid chamber for receiving a fluid is provided. In a further step of providing 1610, a lid substrate with a

added opposite to a fluid chamber opening of the fluid chamber arranged punch opening. In a step of placing 1615, a flexible membrane is placed between the chamber substrate and the lid substrate, with the membrane spanning the die opening and the fluid chamber. In a further step of the production 1620, a channel extending on a side of the membrane facing the chamber substrate is produced which is fluidically connected to the fluid chamber. The step of

Generation 1620 may be performed at a suitable time of the method, for example, prior to the step of providing 1610 the lid substrate, so that in the providing step 1610, the lid substrate having the channel may already be provided. In a step of arranging 1625, a stamp unit is arranged to be formed is to retract into the fluid chamber through the die opening to deflect the membrane into the fluid chamber to allow the fluid to flow out of the fluid chamber into the channel when the fluid in the fluid chamber

Fluid chamber is received.

17 shows a flowchart of a method 1700 for operating a microfluidic device according to one exemplary embodiment. This may be one of the devices described with reference to FIGS. 1 to 5.

In a step of retraction 1705, a stamper unit is retracted into the fluid chamber through the stamper opening to deflect the membrane into the fluid chamber to allow the fluid to flow out of the fluid chamber into the channel when the fluid is received in the fluid chamber. According to one embodiment, the force is exerted by a stamp unit which is actuated in an optional step 1710. The actuation can be done, for example, using a mechanical or

electromechanical actuator are executed.

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.

Claims

claims

A microfluidic device (100) comprising: a chamber substrate (105) having a fluid chamber (110) for

Receiving a fluid (205); a lid substrate (115) having a punch opening (125), the punch opening (125) being disposed opposite a fluid chamber opening (130) of the fluid chamber (110); a flexible membrane (135) disposed between the chamber substrate (105) and the lid substrate (115) and straddling the die opening (125) and the fluid chamber (110); and a punch unit (120) adapted to retract into the fluid chamber (110) through the punch opening (125) to deflect the membrane (135) into the fluid chamber (110)

Outflow of the fluid (205) from the fluid chamber (110)

permit, when the fluid (205) is received in the fluid chamber (110).

2. Device (100) according to claim 1, characterized in that the fluid (205) is received in the fluid chamber (110) and is held by a fluid chamber (110) closing barrier film (200) in the fluid chamber (110) the barrier film (200) is shaped to be opened by the stamp unit (120).

A device (100) according to claim 2, characterized in that the fluid (205) is disposed in a loading container (500) received by the fluid chamber (110), the barrier film (200) closing the loading container (500) , Apparatus (100) according to any one of the preceding claims, characterized in that the fluid (205) is disposed in a blister received from the fluid chamber (110), the blister substantially filling a volume of the fluid chamber (110) the blister is formed to be opened by the stamp unit (120).

Device (100) according to one of the preceding claims, characterized in that a diameter of the punch opening (125) is greater than half the diameter of the

Fluid chamber opening (130).

Device (100) according to one of the preceding claims, characterized by a channel (140) arranged on a

Chamber substrate (105) facing side of the membrane (135) and is fluidly connected to the fluid chamber (110)

Device (100) according to claim 6, characterized in that the diameter of the punch opening (125) is smaller than half the diameter of the fluid chamber opening (130), wherein the punch opening (125) is arranged adjacent to the channel (140).

Device (100) according to claim 7, characterized in that the channel (140) has a channel extension (705) and the

Lid substrate (115) having a vent opening (700) opening into the channel extension (705), the punch opening (125) being disposed between the vent opening (700) and the channel (140), and wherein the membrane (135) is the vent opening (700) not overstretched.

Device (100) according to claim 7, characterized in that the cover substrate (115) has a vent opening (700) which opens into the fluid chamber (110), the punch opening (125) between the vent opening (700) and the channel (140 ), wherein the membrane (135) spans the vent opening (700), and in that the apparatus (100) comprises a further stamp unit (905) adapted to pass through the vent opening (700) into the fluid chamber (110) to deflect the membrane (135) in the fluid chamber (110) to allow an inflow of another fluid into the fluid chamber (110).

Device (100) according to claim 9, characterized in that between the chamber substrate (105) and the membrane (135) an intermediate substrate (900) is arranged, which further a punch opening (125) continuing punch opening (915) and a

Vent further (700) has further vent opening (910) and is formed to a transversely to the vent opening (700) extending and in the further vent opening (910) opening into the air duct (920).

Device (100) according to claim 10, characterized in that the channel (140) between the membrane (135) and the

Intermediate substrate (900) extends and opens into the punch opening (125).

Device (100) according to one of claims 10 to 11, characterized in that a diameter of the fluid chamber opening (130) of the punch opening (125) corresponds, wherein the fluid chamber (110) has a second fluid chamber opening (1105), the diameter of the further vent opening (910).

Device (100) according to one of claims 10 to 12, characterized in that one of the fluid chamber opening (130)

opposing fluid chamber bottom is formed by a further barrier film (1100).

A method (1600) of making a microfluidic device (100), the method comprising the steps of:

Providing (1605) a chamber substrate (105) having a fluid chamber (110) for receiving a fluid (205), Providing (1610) a lid substrate (115) having a

opposite to a fluid chamber opening (130) of the fluid chamber (110) arranged punch opening (125);

Placing (1615) a flexible membrane (135) between the

Chamber substrate (105) and the lid substrate (115), wherein the

Diaphragm (135) straddling the die opening (125) and the fluid chamber opening (130); and

Providing (1625) a stamp unit (120) adapted to retract into the fluid chamber (110) through the die opening (125) to deflect the membrane (135) into the fluid chamber (110) to prevent the fluid (11) from escaping. 205) from the fluid chamber (110) when the fluid (205) is received in the fluid chamber (110).

Method (1700) for operating a microfluidic device (100) according to one of the preceding claims, the method comprising the following step:

Retraction (1705) of the stamp unit (120) of the microfluidic

Apparatus (100) through the die orifice (125) into the fluid chamber (110) of the microfluidic device (100) to deflect the membrane (135) into the fluid chamber (110) to prevent the fluid (205) from leaking out of the fluid chamber (110 ) when the fluid (205) is received in the fluid chamber (110).