DE102006010959A1 - Apparatus for detecting biochemical target molecules, designed to perform all of cell lysis, purification, amplification and detection in a single liquid flow system - Google Patents

Abstract

Apparatus (A) for detecting biochemical target molecules (I) comprises a plate-like conduction element (X) in which are arranged, in a single plane, may channels for transporting a liquid-containing conduction system. Apparatus (A) for detecting biochemical target molecules (I) comprises a plate-like conduction element (X) in which are arranged, in a single plane, may channels for transporting a liquid-containing conduction system. The new features are that (i) X comprises a conduction plate (2) made from injection-molded plastic and an attached sealing system; (ii) a transport opening (9) extends from the conduction system as far as a first upper side (O1) of (2); (iii) a plate-like connection element (3) (made of injection molded plastic) is applied to O1, and (3) has, on a third upper side (O3) corresponding to (9) and facing away from O1, an attachment clip (31) for insertion of the attachment part of a cartridge (7), containing a processing or detection reagent; and (iv) additional packing material (37) is present to ensure a liquid-tight seal between attachment part and (31). An independent claim is included for a method for preparing (A).

Description

The The invention relates to a device for detecting biochemical target molecules The preamble of claim 1. It further relates to a method for the production of the device.

Such a device is from the US 5,229,297 known. The known device consists of two flexible plastic layers, between which a plurality of chambers connected by passages are formed. In some of the chambers, liquids are incorporated to perform a polymerase chain reaction (PCR). The chambers are z. T. sealed with a plastic film which breaks upon exertion of pressure on the wall of the chambers, so that the liquid received therein is pushed out through the opening formed in the passage leading away therefrom. The passageways may also be compressed at certain points to interrupt the passage of fluid.

The known device is disadvantageous in many respects: The Production of fluid-filled chambers is difficult and expensive. When filling The chambers can cause unwanted contamination in it absorbed liquid come. Because of the provision of fluid-filled chambers The known device can only be used to detect certain substances be used. The chambers and passages as well as the closure points the passages allow only a particular predetermined procedure. For a multiple closure through the passages a squeezing this can lead to a leak.

All in all the known device is not very universal; she is also susceptible to interference.

The WO 2005/00279 describes a microfluidic device in which Detection reagents, buffer solutions and the like. Included in disposable cartridges. The disposable cartridges can with the microfluidic device before performing the Reaction be connected. The proposed device allows the Use of with different detection reagents, buffer solutions or Like. Filled Disposable cartridges and is therefore universal. The production of such Microfluidic device is however complicated and expensive.

The WO 03/015922 A1 describes a microreaction chamber whose bottom from a slide is formed. With the interposition of a seal are then laminated to form a microreaction chamber Layers. A cover layer has at least one breakthrough to Connection of a pipette or a syringe for the supply of reaction solutions. The handling of the known device requires skill. When connecting the The pipette or the syringe may be used to introduce contaminants come into the microreaction chamber.

The US 6,391,541 B1 discloses an apparatus for analyzing a liquid sample. In this case, a sample chamber having a mounting part is covered with the interposition of a seal with a lid. On an underside of the mounting part channels are provided, which are closed to form lines with the interposition of a further seal with a closure plate. The known device is relatively complicated and requires a high production cost. When filling the sample into the sample chamber contamination can occur.

task The invention is to the disadvantages of the prior art remove. In particular, it should be a device that is as easy to manufacture as possible which are universally used for the detection of biochemical Target molecules is suitable. Another object of the invention is to specify a possible simple and inexpensive Method for producing the device.

These The object is solved by the features of claims 1 and 39. Advantageous embodiments The invention will become apparent from the features of claims 2 to 38 and 40 to 55.

To proviso The invention provides that the conduit element from a an injection molded plastic circuit board and an associated closure means comprises that of the conduit system line-type breakthroughs extend to a first top of the conduit plate and that at the first top a plate-like, made of an injection-molded Plastic-made connection element is attached, which corresponding to a third upper side applied to the first upper side to the breakthroughs arranged first connection piece for inserting a connection section a processing or Having detection reagent containing cartridge, and that further Sealant for making a liquid-tight joint between the connection sections and the first connection piece are provided.

The proposed device according to the invention comprises a plurality of functionally individualized mounting units, namely a conduit element and a plate-like connection element.

The plate-like design of the Lei tion element and the connection element makes it possible to stack them and thus easily bring in a suitable mounting position. The production, in particular the line plate by injection molding, allows a simple provision of the line-like openings. They do not have to be made separately. The proposed production of the line element and the connection element by injection molding is particularly inexpensive. The assembly is particularly simple due to the complementary plate-like configuration of the conduit plate and the connection element.

By doing the breakthroughs extend to the first top, it is possible with a single assembly step, for example by attaching the Connection element, the sealant in the area of the openings to install. The provision of connecting pieces for the connection of a processing or detection reagent containing cartridge makes the proposed Device particularly universal: Depending on the detection method to be performed Cartridges with the respectively required preparation or Detection reagents are connected to the device. It is special not necessary to fill the device manually. One Entry of contaminations, leaks or maintenance is avoided. It is so far on the disclosure of the WO 2004/096443 A1, the disclosure of which is hereby incorporated by reference becomes. Apart from that leaves using the proposed cartridges the device depending on the nature of the performed Detection method individually with processing or detection reagents assemble. The cartridges can with any volumes of different processing or Detecting reagents filled become. additional Reference is made to WO 2005/002729 A1, the disclosure of which is included herewith.

The Cartridges are each at their opposite the connection section End provided with a piston. By depressing the piston, for example with a pestle, can in the cartridge contained liquid pressed into the pipe system become. This allows a pumping back and forth of liquid. This allows a particularly good mixture of the sample, for example with a buffer or a detection reagent. The Press down the piston can, for example programmatically, with a variety of Pestles take place, so that with it the liquid in the Line system to be moved in a predetermined manner can. For example, in Combination with the proposed device four cylindrical cartridges with a diameter in the range of 5 to 7 mm, preferably 6.1 to 6.5 mm, and six small cylindrical cartridges with a diameter in the range of 2 to 4 mm, preferably 2.8 to 4.2 mm become. The production and filling of such cartridges is inexpensive. The proposed device allows a, in particular chemical or biochemical, processing, a Digestion and / or detection of a large number of samples, substances and target molecules, such as As cells, proteins or nucleic acids.

By the device according to the invention can after attaching the cartridges a microfluidic are formed, in the complex processes, such as B. a digestion of cells, a purification of biomolecules, a nucleic acid amplification and detection of biomolecules can be done. By means of the device according to the invention, it is possible a To realize variety of functions. For example, fluid streams through lines and chambers controlled, valves provided and controlled, liquids mixed and tempered, and chambers for carrying out reactions, for detection and be provided for the storage of waste liquid be. The device according to the invention can be composed of a small number of components. The components can largely or completely made of plastic, in particular by means of an injection molding process, made and assembled in a simple way to the device become. The entire device can be manufactured relatively inexpensively become.

To an advantageous feature of the invention comprises the conduit element a conduit plate and a closure means connected thereto. The allows a particularly simple production of the conduit element.

The closure means may be a film or a closure plate made of plastic, in particular of injection-molded plastic. For example, the conduit plate can form a first upper side of the conduit element for this purpose, and a channel system opening toward the first lower side can be formed on a first lower side opposite the first upper side. In this case, the closure means may cover the channel system. - It may also be that the first underside of the conduit element is substantially flat and on one of the first underside facing the second upper side of the closure plate is formed to the second upper side opening channel system. In both cases, the channels are covered by simply attaching the closure plate to the conduit plate, so that form closed lines. The line system formed from the lines is then accessible only via the line-like openings. The duct system is a system of Variety of lines whose diameter or diagonal in cross-section is usually less than 2 mm, for example 1 mm. The lines can be arranged meandering for the production of long Ver connecting paths. By providing such long communication paths, an increased buffer volume for receiving fluids is provided. Such a buffer volume is required because, when connecting cartridges to the piping system, a pressure spike may occur as a result of which liquid is forced out of the cartridges into the piping system. The buffer volume easily prevents unwanted mixing with liquids which are in adjacent cartridges, in lines or containers of the device.

The Connection of the line and the closure plate, for example by gluing, welding, dissolve of plastic surfaces with suitable solvents or the like. To achieve a durable connection with the aforementioned joining techniques it is useful if the one to be joined Parts are made of the same plastic. Especially dense and pressure-tightly sealed are the lines of the device according to the invention, when the closure means with the conduit plate continuously along from edges provided in the conduit plate and / or in the closure means channels welded is. The lines keep an overpressure of more than 0.5 bar, preferably more than 1 bar, in particular more as 2 bar, stood.

advantageously, the sealant is firmly connected to the connection element. For example, it can be welded to the connection element or be sprayed on it. The connection element can be a structural element include, with which the sealing means are firmly connected. The Structural element can be welded or sealed with the sealing means, for example be sprayed on it. Preferably, the sealant is by 2K injection molding molded on the structural element. This can be a special solid compound and ei ne cost-effective production achieved become. The sealants can with the conduit plate, in particular in an area in which Valves are provided, be welded.

The cable-like breakthroughs can depending on the arrangement and function first, second, third and fourth cable-like breakthroughs include. Likewise, the sealant depending on the configuration and function include first, second and third sealing means.

advantageously, are on an inner wall of the first connecting piece annular first Sealant attached. The provision of the first sealant guaranteed z. B. when connecting a cartridge a tight closure of the device across from the environment and thus ensuring a contamination-free Process management. The annular ones first sealant can have a radially inwardly projecting bead, which merely fixing a terminal portion of an adjacent thereto Cartridge in a first position is used. Fixing the cartridge in the first position allows a manufacturer-side attaching the cartridge without a liquid-conducting Connection to the pipe system, for example by puncturing a closure means the cartridge by one for that provided mandrel, is produced prematurely. The bead is in Essentially circulating executed and preferably has two breaks. The interruptions facilitate insertion of the terminal section and create at the same time a way to escape when pressing the Connecting section compressed air. Furthermore, the first ones Sealant between the bead and the third top one radially inwardly projecting circumferential sealing bead on. The sealing bead is formed circumferentially without interruption and in its diameter so dimensioned that the sealing bead penetrating connection section of the cartridge so tightly closed becomes. When using the device according to the invention, the cartridge from an HMI device from the first position to a second position. In the second position, the terminal portion of the cartridge is opposite to one the device according to the invention surrounding outdoor space liquid-tight completed. At the same time is a liquid-conducting connection produced between the interior of the cartridge and the conduit system.

Furthermore, a second connecting piece with a profile for producing a bayonet closure can be provided on the third upper side. Such a connecting piece allows in a simple manner, for example, the connection of a conventional in the art for taking blood samples Monovette ^® . This eliminates the need to refill a blood sample to be examined, for example, into a pipette or the like. The proposed connection ensures fast, simple and contamination-free process control.

According to an advantageous embodiment, line-like first openings are arranged at least in pairs with a spacing of less than 5 mm, preferably less than 3 mm. Not only two first breakthroughs "in pairs" but also several, for example three, four or five first breakthroughs can be arranged closely adjacent to one another. This can be done by a pair se or group-wise arranged first openings spanning, in particular all around the first openings welded to the conduit plate, membrane a simultaneous optional closure of the first breakthroughs are effected by the membrane is pressed sealingly on the pairs or groups arranged first breakthroughs.

To In a further advantageous embodiment, the first openings are in one at the first top for that arranged first field provided, the first field less than 50%, preferably less than 20%, occupies the first top. It can also several, for example two, first fields can be provided. The summary of the first breakthroughs in one or more first fields a summary of pestles for Control of the thus formed valves. Such a summary the pestle again simplifies the construction of a device for controlling the device according to the invention provided control device.

Conveniently, is a second sealant in the region of a first field after Type of one covering the first field Membrane formed. With such a membrane can simultaneously or arranged in groups first breakthroughs optionally closed become. The proposed membrane thus also forms the closure means for one Variety of valves. With that you can in a particularly simple manner, a plurality of valves in one microfluidic device are manufactured. By an arrangement the first breakthroughs, which allows the membrane to simultaneously seal the closure for one Forms a plurality of valves in one or more first fields, can the number needed Membranes are reduced. This simplifies the production of the Contraption. This is especially the case when the membrane is produced in an injection molding process, as a result, the number the injection molding nozzles and the length the conduction paths are reduced.

To another embodiment open the pairs or groups arranged first breakthroughs respectively in a common provided on the first top, preferably formed as a trough, first recess. The couple or group wise arranged first breakthroughs can each from a rising from the first top be surrounded by ring-like bead. The membrane is expediently surrounding the trough, preferably with the bead, liquid-tight connected, preferably welded. As a result of the proposed circumferential connection forms the membrane together with the trough a chamber. It can, for. B. with a plunger against which the trough open first breakthroughs depressed and thus a closure of the first breakthroughs can be achieved become. When retiring the pestle gives way the membrane back and it is a fluid flow possible through the chamber. With the proposed embodiment is so simple Way fulfills the function of a valve, which by pressing the membrane against the first surface is closable. The proposed valves can without big ones Expense be turned on and allow in the line system a targeted control of the guided in the pipe system fluids. In particular, it is possible the liquids through the piping system into given cartridges or other in the device provided chambers, in particular detection chambers, Purification tank or Reaction vessel to lead.

To a further embodiment opens at least a line-type extending from the line system to the first surface second breakthrough in one of the first top extending first hollow cylinder. Within the first hollow cylinder, a be provided from the first top extending mandrel. Advantageously opens the second breakthrough into the hollow mandrel. - With the Mandrel pierces and seals a cartridge sealing seal thus a fluid connection be made easily with the second breakthrough. It is advantageous that the time of preparation of the liquid compound freely selected and not by the production time of the device is determined. The fluid connection is produced by a feed of the cartridge, by a control unit can be controlled and controlled.

Of the Mandrel can be arranged centrally in the first hollow cylinder. It is but also possible that the thorn off-center is arranged. In an off-center Arrangement hits the mandrel when inserting the cartridges on a off-center Section of the seal. Such an off-center section of the seal usually has a lower elasticity and can thus with a pierced little effort become. The mandrel can be made shorter in this case. In order to One can be between a cartridge's closure means and a bottom the port included dead volume advantageously be reduced. With the proposed seal in combination with the hollow mandrel can safely and reliably Entry of contaminants can be avoided. With such connected cartridges the device forms an outwardly completely closed system. False positive or false negative results can do so safe and reliable be avoided.

To an advantageous embodiment, a diameter and a Height of first hollow cylinder corresponding to the first connecting piece formed so that when attached to the first top connecting element the first connecting piece surrounds the first hollow cylinder and the ring-shaped first sealing means on an inner wall of the first hollow cylinder is applied. This allows a particularly stable and permanently dense design of the first Connecting piece. By the first sealant on the inner wall the first hollow cylinder is applied, the first sealant supported and achieved a permanent sealing effect.

One from the line system to the top extending third breakthrough may be from a second hollow cylinder extending from the first top be surrounded. The second hollow cylinder can, for. B. as a reaction chamber to carry out serve a PCR reaction. The second hollow cylinder may have an inner diameter from 2 to 4 mm, preferably 2.8 to 3.2 mm. Because of the proposed cylinder shape is a uniform temperature of a therein absorbed liquid especially in the implementation a PCR reaction possible. The proposed cylindrical shape has a large surface area and can be effective with a tempered fluid flows around become. The wall thickness the second hollow cylinder is preferably less than 1 mm, preferably less than 0.5 mm, in particular less than 0.3 mm. The low Wall thickness allows a good heat transfer from the fluid to a liquid within the second hollow cylinder. It is also advantageous that the second hollow cylinder protrudes from the conduit plate and thereby largely decoupled thermally from the line system is. As a result, only those in the second hollow cylinder substantially existing liquid heated become. As a result, the thermal inertia of one in the second hollow cylinder formed reaction space over a reduced in the line plate integrated reaction space and Temperature changes in the second hollow cylinder can be completed faster. The second hollow cylinder is therefore particularly good for carrying out a PCR or other nucleic acid amplification reaction suitable, which requires multiple temperature changes.

Of the second hollow cylinder is outward closed with a piston displaceable therein. At a Introduce a PCR fluid in the second hollow cylinder of the piston, preferably by the PCR-liquid to the top, d. H. in the third breakthrough opposite direction, postponed. Eventually when heating the Flüssigkeitsich forming air bubbles go up in the liquid second hollow cylinder upwards. A depression. of the piston allows a promotion the reaction product obtained in a PCR reaction in the second hollow cylinder, for example, in a detection chamber. Preferably, the piston only incomplete down, d. H. in the direction of the third breakthrough, pressed, so that the ascended air bubbles remain in the second hollow cylinder. This prevents the entry of air bubbles into the pipe system become.

To a further embodiment are from the first top extending fasteners, preferably detent springs, snap hooks or the like., Provided for attachment of a detection device. The fastening means are preferably injection-molded on the first surface. Thereby is a low cost and easy manufacture of the device possible. At the detection device it can be a chip with a variety of probes, which are immobilized at defined positions on the chip. By the binding of a target molecule to one of the probes may be a change electrochemical or optical properties at the position of the Probe made and the change captured and thus the target molecule be detected. The proof is carried out without a removal of the chip from the device. The chip may vary depending on the type of Detection method be assembled with different probes. The Vorse hen of locking springs, snap hooks or the like. Enables a easy assembly of a chip. The device can be done easily individually assembled with a suitable chip.

Of Further, one extending from the conduit system to the first top Circular fourth breakthrough from one of the first top be surrounded extending third hollow cylinder. The third hollow cylinder can serve as a digestion chamber, for example, in which a sample is unlocked. The sample can z. As cells, bacteria or Contain viruses. The third hollow cylinder is preferably with a provided in the interior of the hollow cylinder sliding piston. The inventive device is preferably delivered so that the piston immediately located above the fourth breakthrough. By the inflow of a Sample and / or buffer liquid the piston in the fourth breakthrough opposite direction postponed. For digestion, the sample in the digestion chamber be mixed with buffers or detection reagents. The mixture can subsequently between the digestion chamber and a cartridge. and be pumped to order intensive mixing and to achieve a digestion of the sample. The third hollow cylinder has expediently an inner diameter of 4 to 7 mm, preferably 4.8 to 5.2 mm, up.

To Another embodiment of the invention is the conduit system connected to a container extending from the first top. The container can be so big that in it all consumed or no longer used liquids can. He can at one of the bottom of the container opposite side with a Vent vent provided be. The vent can be provided with a source seal, which in contact with liquid the vent closes. A allows such source seal in a simple way, leakage protection; it is inexpensive and easy to assemble.

To A further embodiment of the invention forms at the first Top provided second field the bottom of the detection chamber. A Thickness of the floor is expediently smaller than a thickness of the wiring board. That allows one particularly low-loss heat transport a heat supplied by a heater through the floor in the Detection chamber. Thus, a heating device for heating the Detection chamber simply designed and easy and effective thermal be coupled to the detection chamber.

One Cover of the detection chamber can be formed by the detection device become. The detection device is therefore part of this case the detection chamber.

Of the Lid can be against the floor by a revolving, on a wall attached third sealant be denominated, which to mounted on the connecting element provided circumferential wall is. For mounting the detection device, a plurality of detent springs may be provided, with which the detection device in a against the third sealant Forced position can be locked. That allows one particularly simple installation of the detection device. The lid points on a side facing the conduit plate in the assembled state immobilized probes. Preferably, the lid consists of a break-resistant Material, such. As plastic or a composite material. As special Crosslinked resins are suitable with the carbon electrodes spanning the cover or polymethylmetacry lat (PMMA). The device according to the invention can, depending on the task with a particularly suitable detection device be fitted. Proof of the binding of substances to be detected to the probes takes place preferably optically or electrochemically. -

The First, second and third sealing means may be of the same material be prepared. This allows it to produce the sealant in a shot by injection molding. The shot may expediently be the second shot in 2K injection molding in the production of the connection element act.

The Closure plate has in a the bottom of the detection chamber opposite Section expediently a fourth breakthrough. This allows a particularly close bring up a heater to the ground and thus a particularly effective Heat transfer through the soil in the detection chamber.

To Another particularly advantageous embodiment is a the Connection element at least partially overlapping receiving element for receiving at least one connectable with one of the second openings Cartridge provided. The receiving element is used to guide the Cartridge and expediently a captive recording of the cartridge. For captive recording of Cartridge can on the inside of provided in the receiving element cartridge guides projections or hooks, which at a full insertion the cartridges prevent falling out of the cartridge guides. It is a distance between the protrusions or Hook and provided on the first seal means bead so in the long run The cartridge is matched to the cartridge in the connecting element Used to stand between the bead and the projection or hook is held. It is in particular recorded in the receiving element, that they do not over the receiving element protrudes and accidentally over the pushed through the bead formed resistance against the mandrel and thus prematurely or unintentionally connected to the line system can be.

To the Connecting a cartridge to the piping system is according to the proposed Design only required, the captive in the cartridge guide pressed cartridge into the first port, so the mandrel pierces a seal provided on the cartridge and a terminal portion of the cartridge sealingly on the second sealant is applied. This simplifies the assembly of the device with cartridges. The receiving element can in particular when using photosensitive Detecting reagents have a dark or black color, so that the corresponding cartridges are protected against light. Apart from that, the design of the receiving element facilitates the handling of the proposed device.

The receiving element expediently covers only a portion of the connecting element. The section includes the first field, the second field and the second connecting piece expediently not. The first field is kept free to engage actuating means for moving the first sealing means against the first upper side and the second field for contacting the detection means with an electrical or optical evaluation device.

A housing wall the receiving element may be formed so that between the housing wall and the second hollow cylinder, a slot for performing a Cooling / heating fluid ge is formed. This allows a cyclical warming and cooling off a recorded in the second hollow cylinder liquid, z. B. for performing a PCR reaction. Due to the proposed geometric design of the receiving element can simplifies the geometry of a heater to be connected thereto and thus the manufacture of the heater are cheapened. In particular, on a complicated mechanism for coupling the Heating device be waived. The cooling / heating fluid may be to act on cold / warm air. The second hollow cylinder is expediently for this purpose attached to the edge of the conduit plate. This facilitates a connection of a Cooler / heater.

To In a particularly advantageous embodiment, the line element, preferably the conduit plate and / or the closure plate, from made of an injection-molded plastic. Especially useful it is that at least one, preferably several, are particularly preferred all of the following elements in integral formation with the conduit element, preferably the conduit plate, is / are: mandrel, first Hollow cylinder, second hollow cylinder, third hollow cylinder, detent spring, Container, Centering pin, bottom, bead, chamber. - The proposed production the conduit element made of an injection-molded plastic, in particular polycarbonate, guaranteed a high dimensional stability. By the dimensional stability becomes a precise one Control of liquid flows in the Device allows. Out Plastic injection molded parts can be reasonably priced even in complicated Geometries are produced. It can be in a simple way functional elements, especially in combination with other plastic injection molded parts realize.

To an advantageous embodiment, the conduit plate of a for one Laser beam absorbing first plastic produced. The connection element and / or the closure plate can against one for be made of the laser beam transparent second plastic. The allows insert of the connection element and / or the closure plate by means of laser welding.

The Connection element can be made of a second plastic Comprise structural element. The first, second and third sealing means is expediently from a third, in particular for the laser beam substantially transparent, plastic formed, which in the 2K process on the structural element is injected. This allows a particularly simple and effective production of the connection element. The third plastic is an injection molding process processable elastomer. By injecting the third plastic In 2K injection molding is a particularly reliable and tight connection between the sealing means and the structural element reached. By the structural element is the molded on it Sealant reliable kept in place. As a result, in particular, the assembly simplifies the connection element on the conduit plate.

When particularly useful It turned out that the first and the second plastic, apart from the absorption capacity across from Laser beams, identical and formed in particular of polycarbonate are .. By the way allows but the choice of the same plastic for the first and second plastic a safe and reliable Connecting the mounting elements by means of welding, in particular laser or Orbital welding, or by redemption using solvents or by gluing.

The considered particularly advantageous manufacture of the closure plate, Line plate, the connection element and the receiving element in Injection molding allows a particularly cost-effective Production. It can high quantities with consistently high quality getting produced. Injection molded parts can be manufactured in a clean room become.

The proposed modular design, for example comprising a closure plate, conduit plate, a connection element and receiving element, allows a simple manufacture of the device only using fewer parts. The assembly can be done easily by laser welding, by plugging and / or by snap-in connections. The proposed device can be produced inexpensively, is universal and enables a contamination-free detection of biochemical target molecules. The proposed connection by means of laser welding allows a high production rate, a high degree of automation and ensures a particularly strong and liquid-tight connection of the modules. It can be produced in high quantities with consistently high quality. Apart from that, laser welding can be carried out in the clean room without further ado. Besides, one is optical quality control during or after laser welding possible.

The inventive device is characterized in particular by the fact that it consists of a few assembly elements, namely in particular a conduit element, a connection and a receiving element can be produced. The manufacture of the device from the the aforementioned few mounting elements allows a cost-effective and easy installation. Due to the use of the proposed connection element can be dispensed with a separate assembly of sealing elements.

In order to can considerably costs for saved a separate assembly of sealing elements and / or valves become.

• a) Herstellen eines plattenartigen Leitungselements mit einem darin angeordneten, eine Mehrzahl an in einer Ebene angeordneten Leitungen zum Leiten einer Flüssigkeit aufweisenden Leitungssystem durch Verbinden einer im Spritzgussverfahren aus Kunststoff hergestellten Leitungsplatte mit einem Verschlussmittel und
• b) Anbringen eines im Spritzgussverfahren aus Kunststoff hergestellten Anschlusselements an einer ersten Oberseite des Leitungselements, wobei das Anschlusselement an einer der ersten Oberseite abgewandten dritten Oberseite korrespondierend zu den Durchbrüchen angeordnete erste Anschlussstutzen zum Einstecken eines Anschlussabschnitts einer ein Aufbereitungs- oder Nachweisreagenz enthaltenden Patrone aufweist.

According to another aspect of the invention, a method for producing the device according to the invention is provided with the following steps:

• a) producing a plate-like conduit member having disposed therein, a plurality of arranged in a plane lines for conducting a liquid having conduit system by connecting a manufactured by injection molding of plastic conduit plate with a closure means and
• b) attaching a connection element produced by injection molding of plastic on a first upper side of the conduit element, wherein the connection element on a first upper side facing away from the third upper side corresponding to the apertures arranged first connection piece for inserting a connection portion of a processing or detection reagent containing cartridge.

To the proposed method is the device according to the invention from several assembly units each produced by injection molding produced. Here are some assembly units, in particular the Pipe plate and the connection element, designed like a plate and functionally individualized. It is thus possible in a simple manner, the Mounting elements by stacking to bring in a suitable mounting position and connect. To the Can connect conventional Techniques, such as bonding, dissolving plastic surfaces by means of a suitable solvent, laser welding or the like can be used. Preferably, the connection is made by Laser welding. This makes it possible the assembly units immediately after by an injection molding process Successful production of the conduit plate and the connection element to connect with each other. With the proposed method is a very inexpensive and simple preparation of the inventively proposed microfluidic Cleaning and detection device possible.

To an advantageous embodiment, the closure means is a made of plastic, in particular of injection-molded plastic, produced closure plate or formed from a film. A film can be particularly inexpensive for disposal be put. The provision of an injection molded plastic manufactured closure plate facilitates installation.

advantageously, Be the conduit plate and the closure plate with the step lit. a) by means thereof extending centering pin in a brought predetermined mounting position. Similarly, that too Connection element in step lit. b) by means of the first top extending centering pin in a predetermined mounting position to be brought. This can easily a precise arrangement the mounting elements are achieved to each other.

To In another embodiment, the conduit plate is one for one Laser beam essentially absorbing the first plastic produced. Here is the absorption capacity of the first plastic chosen that it is heated to a temperature in the air by the action of the laser beam Area of the melting temperature is heated. The connection element and the closure plate are expediently made of one for the laser beam made essentially transparent second plastic. The transparency of the second plastic is chosen so that by action the laser beam whose melting temperature is not reached. In order to is a joining of the first and the second plastic manufactured and abutting mounting elements by means of Influence of laser beams possible.

To According to an advantageous embodiment, the connection element comprises a made of the second plastic structural element. The structural element gives the connection element a dimensionally stable structure. On the structural element are according to a particularly advantageous embodiment in 2K injection molding from one, preferably for laser beams essentially transparent, third plastic sealant formed molded. The third plastic is a 2K injection molding process processable elastomer.

With the proposed first, second and third plastics, it is possible to connect the closure means, in particular the closure plate, and / or the connection element to the conduit plate by means of laser welding. It has proved to be particularly useful that the connection of the closure means with the Conduit plate, in particular continuously, along edges of provided in the conduit plate and / or in the closure means channels is performed. This ensures a reliable sealing of the channels and thus the production of dense lines. In particular, the sealing means can also be connected in sections to the line plate by means of laser welding. This can be produced in procedurally simple and efficient manner, a liquid-tight connection between the mounting elements. To realize a valve function, the sealing means in the area around the first recess can be connected to the conduit plate by means of laser welding. In the first recess open the first breakthroughs.

To the step lit. b) can be made of injection-molded plastic Receiving element facing away from the first top third Top of the connection element are attached. The connection element and the receiving element can by means thereof extending centering and locking pin in a brought predetermined mounting position and then locked together become. Thus, the device according to the invention in a few assembly steps finished.

To In another embodiment, then cartridges, which may contain a conditioning or detection reagent, in intended for this purpose Recordings on the receiving element are inserted so that they only at the designated Abutment. The cartridges are on a connection section, For example, with a film, sealed. Im plugged in the shots Condition is the connection section, for example, on an am first bead provided on bead. For the production of a fluid communication between the cartridges and the connecting pieces, these can in a second step pressed into the connecting piece become. It is by the first sealant a safe and reliable Gasket reached. By means of the provided in the connection piece Dorns will simultaneously pierce the seal of the cartridge, so that the liquid contained in the cartridge through the line-like breakthroughs can get into the pipe system.

Of Furthermore, the device can by latching a suitable detection device using the he most of the top extending Locking springs are locked. Depending on the analytical question can differently designed detection devices are kept. It is possible, the invention proposed Device depending on the task individually by selecting a suitable detection device as well as suitable, held in cartridges Reassembling reagents.

In A preferred embodiment of the method is in the second and / or third hollow cylinder in each case a displaceable piston introduced. The piston is preferably in the second hollow cylinder to the third Breakthrough and / or in the third hollow cylinder until the fourth breakthrough advanced.

It it is understood that the above and the following yet to be explained features not only in the specified combinations but also usable in other combinations or even alone are without departing from the scope of the present invention.

following is an embodiment of Invention explained in more detail with reference to the drawings. Show it:

1 an exploded view of the device,

2a a plan view of a first top of the conduit plate according to 1 .

2 B a plan view of a first underside of the conduit plate according to 1 .

2c a sectional view according to the section line BB in 2a .

2d a sectional view along the section line AA in 2c .

2e an enlarged view of the section V in 2d .

2f a sectional view along the section line CC in 2a .

2g a sectional view of a mandrel according to the section line BB in 2a .

3a a top view of a second top of the closure plate,

3b a side view along the section line AA in 3a .

3c a plan view of a second bottom of the closure plate according to 3a .

3d a sectional view along the section line CC in 3a .

4a a top view of a third upper side of a connection element,

4b a top view of a third underside of the connection element,

4c a sectional view along the section line AA in 4a .

4d a sectional view along the section line BB in 4a .

5a a top view of a fourth top of a receiving element,

5b a sectional view along the section line CC in 5a and

5c a plan view of a fourth bottom of the receiving element.

In the 1 The device shown comprises one of a closure plate 1 and a conduit plate 2 formed line element, a connection element 3 , a detection device 4 and a receiving element 5 , With the reference number 6 is a conventional Monovette ^™ for receiving blood and with the reference numeral 7 Generally, cartridges for receiving, for example, buffer solutions, detection reagents, ion exchangers or the like. referred.

The closure plate 1 and the conduit plate 2 and the connection element 3 are suitably made of an injection-molded plastic, preferably made of polycarbonate. The receiving element is preferably made of acrylonitrile / butadiene / styrene (ABS). At the connection element 3 In addition, a made of a plastic material elastic sealant, for example in the 2K process, be sprayed. Advantageously, the conduit plate 2 of a laser substantially impermeable material and the closure plate 1 and the connection element 3 made of a laser transparent plastic. This allows welding of the aforementioned components by means of laser welding. Of course, it is also possible to connect the aforementioned components with other joining techniques, for example by gluing together. At the aforementioned components or mounting elements and mutually corresponding locking elements may be attached. This allows a locking of the mounting elements. After locking, the mounting elements are in a correct mounting position. You can also be connected in this position by further joining techniques, such as welding, especially laser welding together.

The 2a to 2g show in different views the pipe board 2 , At a first bottom U1 are a plurality of channels 8th provided, which form an open to the first bottom U1 channel system. From the channels 8th extend to a first top O1 first line-like openings 9 , The first breakthroughs 9 are arranged in pairs in a first field F1 on the first upper side O1. As in particular from 2e it can be seen, the first breakthroughs open 9 in trough-like first recesses 10 at the first top O1. The first recesses 10 are annularly rising from the first top O1 rising beads 11 surround. At the edge of the first field F1 are extending from the first top O1 first detent springs 12 molded.

Furthermore, first hollow cylinders extend from the first upper side O1 13 , In the middle of each of the first hollow cylinder 13 there is a hollow mandrel extending from the first top O1 14 , The hollow spine 14 is with of the channels 8th extending line-like second openings 15 connected, allowing fluid through the hollow mandrel 14 can flow into the duct or pipe system. The hollow spine 14 is enlarged in 2g shown. The thorn 14 has two tips for piercing a sealing film of a cartridge 7 on. The provision of two tips enables reliable tearing of the closure film and reliably prevents a portion of the closure film from reaching the opening of the hollow mandrel 14 sets, thereby hindering or preventing the passage of fluid.

How out 2d is further apparent, extends from the first upper side O1, a second hollow cylinder 16 that's about a wire-like third breakthrough 17 connected to the conduit system.

On off 2c apparent, also extending from the first top O1 third hollow cylinder l8 is over a wire-like fourth breakthrough 19 with the channels 8th connected. The third hollow cylinder 18 is near the first top O1 partially from a chamber 20 encompassed, which opens to the first bottom U1 out. In the chamber 20 If necessary, a heating medium can be inserted. Further, it is possible to the third hollow cylinder 18 to apply a magnet in order to hold for example magnetic beads in place, to which in turn nucleic acids to be analyzed are bound. This separation of nucleic acids is possible without much effort.

From the first top O1 further extends a container 21 , Several channels 8th open into the container 21 which is used to contain spent reagents, buffer solutions or the like. The Be container 21 has at its upper end in a fourth hollow cylinder 20a opening vent breakthrough 20b on. The fourth hollow cylinder 20a serves to record a source filter. The source filter has the property of swelling on contact with liquid and thus automatically the vent breakthrough 20b to block. As a result, leakage of the liquids received in the device according to the invention into the environment is impossible.

Out 2d It can be seen that from the first top O1 a floor 22 rises, from the line-like fifth breakthroughs 23 to the channels 8th extend. The floor 22 forms a second field F2 on the first top O1. On the ground 22 For example, a chip suitable for the detection of biomolecules can be pressed. The chip snaps through the second detent springs 24 one. He is from the second detent springs 24 so kept that between the ground 22 and the chip forms a space through the fifth breakthroughs 23 can be filled with liquid. The liquid can be detected biomolecules, z. As nucleic acids. For example, nucleic acids can be immobilized on the chip as probes that are complementary to the nucleic acids to be detected.

The 3a to 3d show different views of the closure plate 1 , The closure plate 1 indicates one to the size of the soil 22 corresponding sixth breakthrough 25 on. Seventh breakthroughs 26 serve the engagement in correspondingly designed, provided on the first underside U1 first centering pin 27 , Eighth breakthroughs 28 are made by vertically extending webs 29 divided in two parts.

As in agreement with 1 can be seen, is in the assembled state, a second top O2 of the closure plate 1 on the first underside U1 of the conduit plate 2 at. The closure plate 1 indicates that in the assembled state with the chamber 20 opposite end a second recess 30 on. The second recess 30 is designed so that the closure plate 1 in the assembled state, the opening of the second chamber 20 not covered.

The 4a to 4d show different views of the connection element 3 , From a third top O3 of the connection element 3 extend first connecting pieces 31 and a second connecting piece 32 , A ninth breakthrough 33 is corresponding to the contour of the container 21 designed so that the container 21 in the assembled state, the ninth breakthrough 33 be upheld. In a third field F3 opposite to the first field F1 in the assembled state, there are tenth breakthroughs 34 provided, from the peripheral edge, fourth hollow cylinder 20a extend. A circumferential wall of the fourth hollow cylinder 20a lies in the assembled state in each case the beads 11 across from.

In a fourth field F4 opposite to the second field F2 in the assembled state, there is an eleventh breakthrough formed approximately quadratically 35 intended. A corner of the eleventh breakthrough 35 is formed bevelled. The detection device 4 is corresponding to the shape of the eleventh breakthrough 35 educated. As a result of the slanted formation of one corner of the eleventh breakthrough 35 can the detection device 4 only in one orientation in the eleventh breakthrough 35 be used. The second latching hooks pass through 24 the eleventh breakthrough 35 and at the detection device 4 provided latch hook breakthroughs 35a , A circumferential, corresponding to the contour of the soil 22 trained wall 36 is within the eleventh breakthrough 35 arranged and sections at the edge of the eleventh breakthrough 35 molded.

On an provided with the aforementioned features, made of a transparent plastic structural element, preferably in the 2K process, an elastic sealant molded: The first connecting piece 31 are at their In nenwänden with annular or cylindrical first sealants 37 Mistake. The first sealants 37 are over sprue channels 38 sprayed in the 2K process. A second sealant 39 is formed in the manner of a membrane and covers on a third underside U3 the third field F3 and the tenth openings provided therein 34 , A third sealant 40 is at the inner peripheral edge and the third top O3 of the wall 36 molded. Between the ground 22 , the surrounding wall 36 or the third sealant molded onto it 40 and the means of the second latching hook 24 against the third sealant 40 forced detection device 4 a detection chamber is formed. There is a distance between the floor 22 and the detection device 4 only 100 to 200 μm. The third sealant 40 can, preferably in one-piece design, comprise an inner and an outer sealing ring. The inner sealing ring expediently has a smaller height than the outer sealing ring. Due to the height of the inner sealing ring, the distance between the ground 22 or the detection device 4 be specified reliably. At the same time a reliable sealing effect can be achieved with the outer sealing ring.

The connection element 3 also has twelfth breakthroughs 41 for the passage of the first latching hook 12 and for engagement of the first top O1 of the conduit plate 2 extending second centering pin 42 on.

The 5a to 5c show different views of the receiving element 5 , The receiving element 5 has four first shots 43 for inserting large cartridges 7a and second shots 44 for inserting small cartridges 7b on. At an upper peripheral edge of the openings of the receptacles 43 and 44 are each in opposite arrangement locking lugs 45 molded, with which one in the recording 43 . 44 inserted cartridge 7a . 7b is held captive in it.

As in particular in conjunction with 1 is visible, covers the receiving element 5 in the assembled state, the first connecting pieces 31 and the container 21 , It will be with the receiving element 5 the cartridges 7a . 7b in the recordings 43 . 44 held so that they with their connecting sections in the respective connecting pieces 31 be guided. The receiving element 5 However, does not cover the third F3 and the fourth field F4 and the second hollow cylinder 16 , A housing wall 46 of the receiving element 5 has a concave third recess 47 on, which in the assembled state, the second hollow cylinder 16 partially formed by forming a slot. On a mounting side lower edge of the receiving element 5 are third centering pins 48 provided with which the receiving element 5 by engagement in corresponding recesses on the connection element 3 can be inserted in a predetermined mounting position.

The proposed device can be easily and inexpensively manufactured. This is the closure plate 1 on the first underside U1 of the conduit plate 2 attached by laser welding. The welding preferably takes place continuously along the channels 8th , Furthermore, the connection element 3 by laser welding firmly to the first top O1 of the conduit plate 2 appropriate. To realize dense and stable valves, the welding takes place continuously around the paired or groupwise arranged first openings around between the structural element of the connecting element 3 and the conduit plate 2 and between the sealing means of the connecting element 3 and the conduit plate 2 , The receiving element 5 is achieved by locking with the third top O3 of the connection element 3 connected. Furthermore, the two th and third hollow cylinder are provided with pistons, not shown here.

Subsequently, the thus prepared device - depending on be carried out detection method - with cartridges 7 . 7a . 7b prefabricated, in which the detection reagents, buffer solutions and the like suitable for carrying out the respective method are contained. The device can thus be prefabricated a ready for sale unit.

For detection of certain target molecules then a Monovette 6 in which, for example, a blood sample is contained, on the second connecting piece 32 be connected. It pierces the second connecting piece 32 provided hollow spine 14 a seal in the monovette 6 , so that the blood absorbed therein now through the channels 8th for example in the third hollow cylinder 18 can be pressed. By a suitable control of the diaphragm valves formed in the first field F1 and a predetermined sequence of piston movements in the cartridges 7 then the blood can be incubated with buffers to digest the blood cells contained therein. The aforesaid steps for purifying the sample take place in a purification section of the device. In this purification section, for example, nucleic acids released from the blood corpuscles can be bound to magnetic beads, and interfering compounds, for example proteins or lipids, can be removed by suitable washing steps. To achieve a particularly effective removal of interfering compounds, the magnetic beads can alternately between the third hollow cylinder 18 and a large cartridge connected to its neighborhood 7a be pumped back and forth. Subsequently, the nucleic acids bound to the magnetic beads, for example DNA, can be dissolved by contacting with an elution buffer and subsequently transported on to an amplification section of the device. In the amplification section, the nucleic acids are mixed with reagents to perform the PCR reaction. For this purpose, reagents provided with the nucleic acids can be between two adjacent small cartridges 7b alternately pumped back and forth. The mixture formed can then be in the second hollow cylinder 16 be directed. The second hollow cylinder 16 can then be alternately heated and cooled by flushing a generated with a (not shown here) heating / cooling device hot and cold air, so that a duplication of the nucleic acids according to the principle of PCR reaction takes place.

Subsequently, the solution containing the amplified nucleic acids is conveyed into a detection section of the device. In this case, the solution may be admixed with a suitable buffer which accelerates a hybridization reaction and non-specific bonds to the electrode detection device 4 suppressed. Alternatively, mixing with the aforementioned buffer may be accomplished by alternating reciprocating between two cartridges 7a . 7b respectively.

Subsequently, the solution is passed into the detection chamber, which is detected by the detection device 4 is covered. A distance between the ground 22 and the at the detection device 4 provided the ground 22 facing electrodes is only 100 to 200 microns. There can be up to 100 electrodes on the detection device 4 be provided. Each of the electrodes may be coated with a specific probe which can hybridize with the amplified nucleic acids. If complementary nucleic acids are contained in the solution with the probes, a double-stranded nucleic acid is formed. By means of a washing buffer, non-complementary nucleic acids are removed from the surface of the detection means occupied by the electrodes 4 rinsed. This ensures that in a subsequent measurement process only specifically bound nucleic acids can be detected by electrochemical measurement signals at the electrodes. From the detected signals, the presence of a specific nucleic acid can be detected.

To maintain a constant temperature, a heating medium may be applied to the first underside U1 of the conduit plate 2 in the area of the soil 22 through the sixth breakthrough 25 be introduced.

Spent buffer solutions, detection reagents and the like can pass through the channels 8th in the container 21 be transferred. The container 21 has a vent opening, which is provided with a source seal, which closes the vent opening in contact with liquid. On the one hand, this ensures that no solutions escape from the device into the environment. On the other hand, entrainment of contaminants in the device can be prevented.

1

closing plate

2

conducting plate

3

connecting element

4

detection means

5

receiving element

6

monovette

7

cartridge

7a

big cartridge

7b

small cartridge

8th

channel

9

first breakthrough

10

first recess

11

bead

12

first detent spring

13

first hollow cylinder

14

mandrel

15

second breakthrough

16

second hollow cylinder

17

third breakthrough

18

third hollow cylinder

19

fourth breakthrough

20

chamber

20a

fourth hollow cylinder

20b

Venting breakthrough

21

container

22

ground

23

fifth breakthrough

24

second detent spring

25

sixth breakthrough

26

seventh breakthrough

27

first spigot

28

eight breakthrough

29

web

30

second recess

31

first spigot

32

second spigot

33

ninth breakthrough

34

tenth breakthrough

35

eleventh breakthrough

35a

Locking hooks breakthrough

36

wall

37

first sealant

38

runner

39

second sealant

40

third sealant

41

twelfth breakthrough

42

second spigot

43

first admission

44

second admission

45

locking lug

46

housing wall

47

third recess

48

third spigot

F1

first field

F2

second field

F3

third field

F4

fourth field

O1

first top

O2

second top

O3

third top

U1

first bottom

U2

second bottom

U3

third bottom

Claims (55)

Device for detecting biochemical target molecules, comprising a plate-like conducting element with a plurality of lines arranged therein ( 8th ) for conducting a liquid-containing conduit system, characterized in that the conduit member made of an injection-molded plastic conduit plate ( 2 ) and a closure means connected thereto, that line-like openings ( 9 ) to a first top (O1) of the conduit plate ( 2 ) that on the first upper side (O1) a plate-like, made of an injection-molded plastic connecting element ( 3 ) attached to which egg ner of the first upper side (O1) facing away from the third upper side (O3) corresponding to the openings ( 9 ) arranged first connecting piece ( 31 ) for inserting a terminal portion of a cartridge containing a processing or detection reagent ( 7 . 7a . 7b ), and further that sealant ( 37 . 39 . 40 ) for producing a liquid-tight connection between the connection sections and the first connecting piece ( 31 ) are provided. Apparatus according to claim 1, wherein the closure means comprises a film or a closure plate made of plastic, in particular of injection-molded plastic ( 1 ). Device according to one of the preceding claims, wherein on one of the first upper side (O1) of the conduit plate ( 2 ) opposite the first lower side (U1) is formed a channel opening which opens towards the first lower side (U1). Device according to one of the preceding claims, wherein the closure means covers the channel system. Device according to one of claims 2 to 4, wherein the first underside (U1) of the conduit element substantially flat and on one of the first underside (U1) facing the second upper side (O2) of the closure plate ( 1 ) is formed to the second top (O2) towards opening channel system. Device according to one of the preceding claims, wherein the sealing means ( 37 . 39 . 40 ) fixed to the connection element ( 3 ) connected is. Device according to one of the preceding claims, wherein on an inner wall of the first connecting piece annularly formed first sealing means ( 37 ) are mounted. Device according to one of the preceding claims, wherein at the third upper side (O3) a second connecting piece (O3) 32 ) is provided with a profile for producing a bayonet closure. Device according to one of the preceding claims, wherein line-like first openings ( 9 ) are arranged in pairs or in groups with a distance of less than 5 mm, preferably less than 3 mm. Device according to one of the preceding claims, wherein the first breakthroughs ( 9 ) are arranged in a first field (F1) provided for this purpose on the first upper side (O1), the first field (F1) occupying less than 50%, preferably less than 20%, of the first upper side (O1). Device according to one of the preceding claims, wherein second sealing means ( 39 ) is formed in the region of the first field (F1) in the manner of a membrane covering the first field (F1). Device according to one of the preceding claims, wherein the paired or groupwise arranged first breakthroughs ( 9 ) each in a common on the first top (O1) provided, preferably as a trough ( 10 ) formed, first recess ( 10 ) to open. Device according to one of the preceding claims, wherein the paired first breakthroughs ( 9 ) each from a rising from the first top (O1) ring-like bead ( 11 ) are surrounded. Device according to one of the preceding claims, wherein the membrane circumferentially around the trough, preferably with the bead ( 11 ), liquid-tight connected, preferably welded, is. Device according to one of the preceding claims, wherein at least one of the line system to the first top (O1) extending line-like second breakthrough ( 15 ) in a first hollow cylinder extending from the first upper side (O1) ( 13 ) opens. Device according to one of the preceding claims, wherein within the first hollow cylinder ( 13 ) a mandrel extending from the first top (O1) ( 14 ) is provided. Device according to one of the preceding claims, wherein the second breakthrough ( 15 ) in the hollow mandrel ( 14 ) opens. Device according to one of the preceding claims, wherein a diameter and a height of the first hollow cylinder ( 13 ) corresponding to the first connecting piece ( 31 ) are formed, so that when mounted on the first top (O1) connecting element ( 3 ) the first connecting piece ( 31 ) the first hollow cylinder ( 13 ) and the annular first sealant ( 37 ) on an inner wall of the first hollow cylinder ( 13 ) is present. Device according to one of the preceding claims, wherein a line-like third opening extending from the line system to the first upper side (O1) ( 17 ) of a second hollow cylinder extending from the first upper side (O1) ( 16 ) is surrounded. Device according to one of the preceding claims, wherein fastening means extending from the first upper side (O1), preferably detent springs ( 12 . 24 ), for attaching a Nachwei device ( 4 ) are provided. Device according to one of the preceding claims, wherein a from the line system to the first top (O1) he stretching stray fourth breakthrough ( 19 ) of a fourth hollow cylinder ( 18 ) is surrounded. Device according to one of the preceding claims, wherein the conduit system with a container extending from the first upper side (O1) ( 21 ) connected is. Device according to one of the preceding claims, wherein a second panel (F2) provided on the first upper side (O1) covers the floor ( 22 ) forms a detection chamber. Device according to one of the preceding claims, wherein a cover of the detection chamber by the detection means ( 4 ) is formed. Device according to one of the preceding claims, wherein the cover against the ground ( 22 ) by a circulating, third sealant ( 40 ) is sealed, which at one of the connection element ( 3 ) provided circumferential wall ( 36 ) is attached. Device according to one of the preceding claims, wherein the closure plate ( 1 ) in a ground ( 22 ) the detection chamber opposite section a sixth breakthrough ( 25 ) having. Device according to one of the preceding claims, wherein the connection element ( 3 ) at least partially covering receiving element ( 5 ) for receiving at least one with one of the second breakthroughs ( 15 ) connectable cartridge ( 7 . 7a . 7b ) is provided. Device according to one of the preceding claims, wherein the receiving element ( 5 ) only a portion of the connecting element ( 3 ) covered. Device according to one of the preceding claims, wherein the section the first field (F1), the second field (F2) and the second connecting piece ( 32 ) not included. Device according to one of the preceding claims, wherein a housing wall ( 46 ) of the receiving element ( 5 ) is formed so that between the housing wall ( 46 ) and the second hollow cylinder ( 16 ) is formed a slot for performing a cooling / heating fluid. Device according to one of the preceding claims, wherein at least one, preferably several, in particular all, of the following elements in one-piece construction with the conduit element, preferably the conduit plate ( 2 ), is / are: spike ( 14 ), first hollow cylinder ( 13 ), second hollow cylinder ( 16 ), third hollow cylinder ( 18 ), Detent spring ( 12 . 24 ), Container ( 21 ), Centering pins ( 27 ), Ground ( 22 ), Bead ( 11 ). Device according to one of the preceding claims, wherein the conduit plate ( 2 ) is made of a first plastic substantially absorbing a laser beam. Apparatus according to claim 32, wherein the connection element ( 3 ) and / or the closure plate ( 1 ) is made of a substantially transparent to the laser beam plastic / is. Device according to one of the preceding claims, wherein the closure plate ( 1 ) and / or the connecting element ( 3 ) by laser welding with the conduit plate ( 2 ) is / are connected. Device according to one of the preceding claims, wherein the closure means with the conduit plate ( 2 ) continuously along edges of in the conduit plate ( 2 ) and / or channels provided in the closure means ( 8th ) is welded. Device according to one of the preceding claims, wherein the connecting element ( 3 ) comprises a structural element made of the second plastic. Device according to one of the preceding claims, wherein the first ( 37 ), second ( 39 ) and third sealants ( 40 ) is formed from a, in particular for the laser beam substantially transparent, third plastic, which is molded in the 2K process on the structural element. Device according to one of the preceding claims, wherein the first and the second plastic identical and in particular made Polycarbonate are formed. Method for producing a device according to one of the preceding claims, comprising the following steps: a) producing a plate-like conducting element with a plurality of lines arranged in a plane ( 8th ) for conducting a liquid-containing conduit system by connecting a plastic injection-molded line plate ( 2 ) with a closure means and b) attaching a connection element produced by injection molding from plastic ( 3 ) at a first top (O1) of the conduit element, where at the connecting element on a third upper side (O3) facing away from the first upper side (O1), corresponding to the openings ( 9 ) arranged first connecting piece ( 31 ) for inserting a terminal portion of a cartridge containing a processing or detection reagent ( 7 . 7a . 7b ) having. A method according to claim 39, wherein the closure means comprises a closure plate made of plastic, in particular of injection-molded plastic (US Pat. 1 ) or is formed from a film. A method according to claim 39 or 40, wherein the conduit plate ( 2 ) and the closure plate ( 1 ) at step lit. a) by means of extending centering pin ( 27 ) are brought into a predetermined mounting position. Method according to one of claims 39 to 41, wherein the connecting element ( 3 ) at step lit. b) by means of the first upper side (O1) extending centering pin ( 42 ) is brought into a predetermined mounting position. Method according to one of claims 39 to 42, wherein the conduit plate ( 2 ) is made of a first plastic substantially absorbing a laser beam. Method according to claim 43, wherein the connecting element ( 3 ) and the closure plate ( 1 ) are made of a second plastic substantially transparent to the laser beam. Method according to one of claims 39 to 44, wherein the connecting element ( 3 ) comprises a structural element made of the second plastic. Method according to one of claims 39 to 45, wherein on the structural element in 2K process from a, preferably transparent to laser beams substantially transparent, third plastic sealant formed ( 37 . 39 . 40 ) are sprayed. Method according to one of claims 39 to 46, wherein the closure means, in particular the closure plate ( 1 ), and / or the connecting element ( 3 ) by laser welding with the conduit plate ( 2 ) get connected. Method according to one of claims 39 to 47, wherein the joining of the closure means to the conduit plate ( 2 ), in particular continuously, along edges of in the conduit plate ( 2 ) and / or channels provided in the closure means ( 8th ) is carried out. Method according to one of claims 39 to 48, wherein the sealing means ( 37 . 39 . 40 ) in sections by means of laser welding with the conduit plate ( 2 ) get connected. A method according to any one of claims 39 to 49, wherein the sealants ( 37 . 39 . 40 ) around the first recess ( 10 ) are connected by laser welding to the circuit board around. Method according to one of claims 39 to 50, wherein after step lit. b a receiving element made of injection-molded plastic ( 5 ) on one of the first upper side (O1) facing away from the third upper side (O3) of the connecting element ( 3 ) is attached. Method according to one of claims 39 to 51, wherein the connecting element ( 3 ) and the receiving element ( 5 ) by means of extending centering and locking pin ( 48 ) are brought into a predetermined mounting position and then locked together Method according to one of claims 39 to 52, wherein cartridges ( 7 . 7a . 7b ) in dedicated shots ( 43 . 44 ) on the receiving element ( 5 ) are inserted so that they only at the designated 31 ) issue. Method according to one of claims 39 to 53, wherein a detection device ( 4 ) using latching hooks extending from the first upper side (O1) ( 12 ) is locked. A method according to any one of claims 39 to 54, wherein in the second and / or third hollow cylinder in each case a displaceable therein Piston introduced becomes.