WO2023016937A1

WO2023016937A1 - Microfluidic device, method for producing a microfluidic device, and method for operating a microfluidic device

Info

Publication number: WO2023016937A1
Application number: PCT/EP2022/072075
Authority: WO
Inventors: Daniel Sebastian Podbiel
Original assignee: Robert Bosch Gmbh
Priority date: 2021-08-12
Filing date: 2022-08-05
Publication date: 2023-02-16
Also published as: DE102021208823A1

Abstract

The invention relates to a microfluidic device (300) for analyzing sample material. The device (300) has a carrier device (100) which is formed with a microfluidic network (105) for processing the sample material. The microfluidic device also has at least one sample loading chamber (110) which is arranged on the carrier device (100) and at least one additional sample loading chamber (120) which is arranged on the carrier device (100). The device (300) additionally comprises either at least one cover device (200) for at least partly covering the carrier device (100), said cover device (200) being designed to cover the sample loading chamber (110), or at least one other cover device for at least partly covering the carrier device (100), said other cover device being designed to cover the additional sample loading chamber (120).

Description

title

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

State of the art

The invention is based on a microfluidic device, a method for producing a microfluidic device and a method for operating a microfluidic device according to the species of the independent claims. The subject matter of the present invention is also a computer program.

Microfluidic analysis systems, so-called lab-on-chips, LoCs for short, allow automated, reliable, fast, compact and cost-effective processing of patient samples for medical diagnostics. By combining a large number of operations for the controlled manipulation of fluids, complex molecular diagnostic test sequences can be carried out on a so-called lab-on-chip cartridge, which can alternatively also simply be referred to as a cartridge or as a microfluidic device. Lab-on-chip cartridges can, for example, be manufactured inexpensively from polymers using series production processes such as injection molding, stamping or laser transmission welding.

Disclosure of Invention

Against this background, with the approach presented here, a microfluidic device, a method for producing a microfluidic device and a method for operating a microfluidic device, Furthermore, a control unit that uses this method and, finally, a corresponding computer program according to the main claims are presented. Advantageous developments and improvements of the device specified in the independent claim are possible as a result of the measures listed in the dependent claims.

The microfluidic device presented here, which can also be referred to as a lab-on-chip cartridge, can advantageously be used to analyze different sample types and can also be individualized in a particularly simple and cost-effective manner in order to ensure that a defined sample type is correctly entered into the lab -on-chip cartridge by a user to favor. The individualization of the device enables a particularly safe and reliable input of precisely one type of sample into the lab-on-chip cartridge.

A microfluidic device for analyzing sample material is presented, the device having a carrier device which is designed with a microfluidic network for processing the sample material, as well as at least one sample input chamber arranged on the carrier device and at least one further sample input chamber arranged on the carrier device. In addition, the device comprises at least one cover device to at least partially cover the carrier device, the cover device being designed to cover the sample input chamber (and leave the further sample input chamber free or accessible), or at least one further cover device to at least partially cover the carrier device, wherein the further cover device is designed to cover the further sample input chamber (and leave the sample input chamber free or accessible). In other words, the core of the invention is a lab-on-chip cartridge consisting of a carrier device, which can also be referred to as a universal microfluidic device, with at least two different sample input chambers, each designed in an optimized manner for the input of at least one sample type could be. This carrier device can be combined with at least two different covering devices, depending on the selected covering device at least two different sample input chambers for the input of at least one sample can be used by a user. In this case, for example, the first sample input chamber can be accessible to a user for inputting a sample, while the at least one second sample input chamber is covered by the selected covering device. If, on the other hand, the carrier device is combined with the other cover device, the first sample input chamber can be covered by the additional cover device, while the second sample input chamber can be accessible for a user to input a sample. “Being accessible” can in particular also be understood to mean that the covering device or the further covering device has a movable cover for the further sample input chamber or for the sample input chamber for the input of a sample. According to a particular embodiment, each of the two cover devices thus covers at least one of the sample input chambers and leaves at least one of the sample input chambers accessible for inputting a sample, with the cover devices not covering the same sample input chambers. The covering device and the further covering device can also be referred to as covering elements or covering devices. It is also conceivable that the covering device and/or the further covering device is/are detachably fastened or can be fastened to the carrier device, for example via a form-fitting connection such as a clip connection. In an alternative embodiment, the covering device and/or the further covering device is firmly connected to the carrier device, for example glued or welded, and can then preferably no longer be detached from the carrier device without being destroyed. In general, different types of sample material or sample substances are suitable for a molecular diagnostic analysis of a sample substance within a lab-on-chip cartridge. In addition to liquid samples in which the species to be detected are present in an aqueous environment, there are also swab samples, for example, in which the sample substance can be present in a form attached to a sampling device, for example a so-called swab or flocked swab. To the sample material with the species to be detected in the microfluidic To convert the system, lab-on-chip cartridges usually have at least one sample input chamber, which is used to input the sample material. Depending on the type of sample, it is advantageous to use different sample input chambers, each of which is specially tailored to a specific type of sample, for example to allow the user to input the sample substance into the lab-on-chip cartridge in a particularly simple and reliable manner and additionally or alternatively to achieve a particularly high extraction efficiency in the microfluidic transfer of the sample material from the input sample into the microfluidic system. The microfluidic device presented here advantageously offers a further sample input chamber in addition to the regular one sample input chamber, so that, for example, different sample types can be transferred to the microfluidic network and processed using the same device. By covering one sample input chamber in each case with the covering device, it is also advantageously possible to avoid using the wrong sample input chamber for a specific sample type, for example due to a user error. Due to the presence of only one sample entry opening in the device, it is advantageously possible to achieve particularly simple handling when entering the sample into the device. In particular, it can be sufficient to just close one cover element, in contrast to a cartridge with at least two separate sample input openings, which each have to be closed separately from one another, in particular after only exactly one sample has been input into the device. Accordingly, the product perception of the user can also be improved by the approach presented here. In other words, with the device presented here, exactly one universal variant of a lab-on-chip cartridge is advantageously sufficient in order to be able to analyze different sample types with it. Although a somewhat higher complexity of the lab-on-chip cartridge is accepted in this way, the variety of variants of the individual components for forming the lab-on-chip cartridge can be reduced. According to one embodiment, the sample input chamber can be designed to input a liquid sample and additionally or alternatively the further sample input chamber can be designed to input a swab sample. The sample input chamber and the further sample input chamber can be designed, for example, to transfer different types of samples into the microfluidic network of the carrier device. The different sample types can be, for example, a liquid sample on the one hand and a swab sample on the other, which can initially be present in a form attached to a sampling device, which can also be referred to as a swab or flocked swab. For example, in an advantageous embodiment, the sample input chamber for a liquid sample can have a circular opening, for example on the upper side of the sample input chamber, to enable the liquid sample to be introduced into the device particularly easily and safely, for example using a pipette. The liquid sample can be, for example, an aqueous solution, for example obtained from a biological substance, for example of human origin, such as a body fluid, a smear, a secretion, sputum, a tissue sample or a device with attached sample material. For example, species of medical, clinical, diagnostic or therapeutic relevance such as bacteria, viruses, cells, circulating tumor cells, cell-free DNA, proteins or other biomarkers or in particular components from the objects mentioned can be found in the sample liquid. The further sample input chamber for a swab sample, which can be present in a form connected to a sampling device, can in an advantageous embodiment, for example, have a geometric shape that is optimized with regard to the sampling device, which is advantageously suitable for removing the sample material from the sampling device microfluidically to release. For example, the sampling device can be a so-called swab or flocked swab with an attached swab sample, for example a nose and throat swab (nasopharynx swab), a wound swab or a vaginal swab. Species of medical, clinical, diagnostic or therapeutic relevance, such as bacteria, viruses, cells, cell-free DNA, proteins or other biomarkers or in particular components from the objects mentioned are located. In addition, the further sample input chamber can have elements, for example, which can guide the sampling device when it is input into the device, in order to enable a particularly defined and safe input of the sampling device with the swab sample into the device. This has the advantage that different sample material or different sample types can be input into the microfluidic device for carrying out different analysis processes.

According to a further embodiment, the covering device and the further covering device can have the same external dimensions within a tolerance range. For example, the covering device and the further covering device can be of such a similar nature that they can advantageously be used on the same production line and can be combined with the carrier device previously produced, for example, using the same production robot. For this purpose, the cover elements can have comparable external dimensions, for example, with a tolerance range of 2%, for example. Additionally or alternatively, the covering device and the further covering device can have, for example, a comparable set of latching elements which, for example, can allow exactly one of the covering devices to latch into the same carrier device.

According to a further embodiment, the device can comprise at least one combination element for mechanically connecting the carrier device to the covering device and additionally or alternatively to the further covering device. For example, the carrier device can have special combination elements, which can be designed to create a tight mechanical connection with the cover elements. For example, these can be latching elements which can advantageously allow at least one cover element to latch securely and possibly irreversibly into the carrier device. In this advantageous way, on the one hand, a simple mechanical Connection of the carrier device to the covering device and the further covering device can be achieved and, on the other hand, it can be prevented that the covering elements are unintentionally detached or can be detached from the carrier device.

According to a further embodiment, the covering device and additionally or alternatively the further covering device can comprise a closure element for reversibly closing the sample input chamber and additionally or alternatively the further sample input chamber. For example, a movable closure element can be integrated in the cover device and additionally or alternatively in the further cover device, which can enable the user to close a sample input opening, for example after sample material has been input into the sample input chamber or the further sample input chamber.

This advantageously enables the user to handle the lab-on-chip cartridge particularly easily when closing the sample input chamber or the additional sample input chamber, since in particular no closing element present separately from the device may be required to close the sample input chamber.

In addition, the cover device can have at least one closure element arranged on the closure element for irreversibly closing the closure element. For example, the closing element can be at least one further latching element.

Advantageously, by implementing the closing element in the cover element, the sample input chamber and additionally or alternatively the further sample input chamber can be closed securely and irreversibly.

According to a further embodiment, the covering device and additionally or alternatively the further covering device can have at least one information element for providing device-specific information. For example, the covering device and additionally or alternatively the further covering device can each have at least one piece of individualized information. The information can, for example, as a graphic Information in the form of symbols that can be interpreted by a user, such as letters and additional or alternative pictograms. Advantageously, the information element can be used to show the user, for example, the type of sample to be used in combination with the lab-on-chip cartridge and, if appropriate, the correct input of the sample into the lab-on-chip cartridge. In a further particularly advantageous embodiment, the information element can be machine-readable information, such as a QR code, a data matrix code, a bar code and additionally or alternatively information that can be transmitted via RFID. This can be present, for example, on the cover device and the further cover device in order to advantageously transfer the exact cartridge type to an analysis device, which can be designed for processing the lab-on-chip cartridge, for example, and to carry out a sample-type-specific flow log make possible.

According to a further embodiment, the device can comprise a reservoir for providing reagents to the device, wherein the reservoir can have at least one information unit for providing at least one piece of reagent-specific information. For example, the carrier device can include a storage container in the form of a so-called reagent bar, which can be provided for combination with individual liquid reagents. For example, up to three different liquid reagents can be enclosed in a reagent bar in three foil-sealed liquid reagent storage chambers per device. The reagent bar can, for example, contain an assortment of liquid reagents which can be intended for processing a sampling device inserted into the device. Additionally or alternatively, the reagent bar can contain, for example, a compilation of liquid reagents, which can be provided for processing a liquid sample entered into the device. The information unit can be designed to provide a user with information about the reagents contained in the reagent bar. In addition to designating the liquid reagents present, it is also possible, for example, to use a data matrix code For example, a batch designation and additionally or alternatively information for filling the reagents can be provided. The information can advantageously be called up during the manufacture of the lab-on-chip cartridge in order to ensure that the carrier device is fitted with the correct liquid reagents in each case.

According to a further embodiment, the device can comprise an evaluation chamber for evaluating sample material, it being possible for the evaluation chamber to be fluidically connected or connectable to the sample input chamber and the further sample input chamber. The evaluation chamber can, for example, comprise a chip with an array of microcavities, specific reagents, for example, being able to be stored upstream in the microcavities, which can enable detection of different targets, for example in a liquid. An analysis or an evaluation of the sample material entered into the sample input chamber and into the further sample input chamber can thus advantageously take place.

According to one embodiment, a microfluidic system can also be provided with a variant of a microfluidic device with the covering device and the further covering device that is presented here. In other words, the system comprises a carrier device as described above and at least one cover device described above and one further cover device described above, wherein one of the two cover devices can already be arranged on the carrier device. For example, the carrier device together with the cover device and the further cover device can be packaged in a common packaging unit, for example a bag or box, so that a user of the microfluidic system can apply the appropriate cover unit to the carrier device quickly and depending on the application scenario. This creates a microfluidic system that can be used very flexibly.

In addition, a method for producing a variant of the microfluidic device presented above is presented. The method includes a step of providing the carrier device and the covering device is designed to cover the sample input chamber, and a step of covering at least part of the carrier device with the cover device, the sample input chamber being covered by the cover device. In addition, the method comprises a step of providing a further copy of the carrier device and the further covering device, which is designed to cover the further sample input chamber of the further copy of the carrier device, and a step of covering at least part of the further copy of the carrier device with the further covering device , wherein the further sample input chamber of the further copy of the carrier device is covered by the further covering device. Advantageously, a particularly simple and inexpensive individualization of the microfluidic device and a safe and particularly simple use of the device by the user can be made possible using this method. By individualizing the device using at least one cover element, which is only applied in the last manufacturing step, a largely standardized manufacture of the device is possible. In particular, for example, a production line can be used to first produce a universal microfluidic device, and only then in the last step can an individualized cover element be applied to the universal microfluidic device, which can bring about the individualization of the device to at least one predetermined sample type. By using a universal carrier device, the number of parts required for the production of lab-on-chip cartridges with individualized sample input can be significantly reduced. In particular, the same components/semi-finished products can be used for the production of the carrier device, regardless of the individualization ultimately selected, only the cover element should be applied to the universal microfluidic device in an individualized form. In this way, the additional production costs that arise for the variants of the microfluidic device with an individualized sample input can be significantly reduced. The development costs can also be minimized since, in addition to the carrier device, only the cover elements specific to the sample type are developed individually. In addition, a method for using a variant of the microfluidic device presented above is presented, the method comprising a step of receiving the device in an analysis device and a step of processing sample material entered into the sample input chamber or into the further sample input chamber.

According to one embodiment, an evaluation step can be provided in the method, in which sample material brought from the sample input chamber and additionally or alternatively from the further sample input chamber into the evaluation chamber can be evaluated.

These methods can be implemented, for example, in software or hardware or in a mixed form of software and hardware, for example in a control unit.

The approach presented here also creates a control device that is designed to carry out, control or implement the steps of a variant of a method presented here in corresponding devices. The object on which the invention is based can also be achieved quickly and efficiently by this embodiment variant of the invention in the form of a control unit.

For this purpose, the control device can have at least one computing unit for processing signals or data, at least one memory unit for storing signals or data, at least one interface to a sensor or an actuator for reading in sensor signals from the sensor or for outputting control signals to the actuator and/or or have at least one communication interface for reading in or outputting data that are embedded in a communication protocol. The arithmetic unit can be, for example, a signal processor, a microcontroller or the like, with the memory unit being able to be a flash memory, an EEPROM or a magnetic memory unit. The communication interface can be designed to read in or output data wirelessly and/or by wire, with a communication interface that is by wire Can read or output data, read this data, for example, electrically or optically from a corresponding data transmission line or can output it in a corresponding data transmission line.

In the present case, a control device can be understood to mean an electrical device that processes sensor signals and outputs control and/or data signals as a function thereof. The control unit can have an interface that can be designed in terms of hardware and/or software. In the case of a hardware design, the interfaces can be part of what is known as a system ASIC, for example, which contains a wide variety of functions of the control device. However, it is also possible for the interfaces to be separate integrated circuits or to consist at least partially of discrete components. In the case of a software design, the interfaces can be software modules which are present, for example, on a microcontroller alongside other software modules.

A computer program product or computer program with program code, which can be stored on a machine-readable carrier or storage medium such as a semiconductor memory, a hard disk memory or an optical memory and for carrying out, implementing and/or controlling the steps of the method according to one of the embodiments described above, is also advantageous used, especially when the program product or program is run on a computer or device.

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

1 shows a schematic plan view illustration of a carrier device according to an embodiment;

2A shows a schematic top view representation of a covering device according to an embodiment; 2B shows a schematic top view representation of a further covering device according to an embodiment;

3 shows a schematic top view representation of a microfluidic device according to an embodiment;

FIG. 4 shows a schematic top view representation of a microfluidic device according to an embodiment; FIG.

FIG. 5 shows a schematic top view representation of a storage container according to an embodiment; FIG.

6 shows a schematic top view illustration of an embodiment of a carrier device with a storage container;

FIG. 7 shows a flow chart of a method for producing a microfluidic device according to an embodiment; FIG.

FIG. 8 shows a flow chart of a method for producing a microfluidic device according to an embodiment; FIG.

FIG. 9 shows a flow diagram of a method for using a microfluidic device according to an embodiment; FIG. and

10 shows a schematic representation of an exemplary embodiment of an analysis device for accommodating a microfluidic device.

In the following description of favorable exemplary embodiments of the present invention, the same or similar reference symbols are used for the elements which are shown in the various figures and have a similar effect, with a repeated description of these elements being dispensed with.

1 shows a schematic top view representation of a carrier device 100 according to an embodiment. The carrier device 100 is equipped with a microfluidic network 105 designed for processing sample material and for this purpose comprises, for example, a sample input chamber 110 and a further sample input chamber 120. In another exemplary embodiment, the carrier device, which can also be referred to as a universal microfluidic device, can have a variable number of different sample input chambers. In the advantageous embodiment of the microfluidic network 105 shown, the two sample input chambers 110, 120 are implemented symmetrically in the microfluidic network 105, so that each of the two sample input chambers 110, 120 can be used in a comparable manner for inputting a sample. Accordingly, either the sample input chamber 110 or the further sample input chamber 120 can be used in order to perform microfluidic processing of the input sample material within the microfluidic network 105 . Depending on the sample input chamber 110, 120 used, only a special flow protocol is required, whereas the same microfluidic network 105 can be used in both cases. In this exemplary embodiment, the sample input chamber 110 is designed to be optimized for the input of a liquid sample, merely by way of example. In contrast to this, the further sample input chamber 120 is designed merely by way of example for the input of a sampling device (swab or flocked swab) with attached sample material, ie for inputting a swab sample. For this purpose, the further sample input chamber 120 for inputting a sampling device includes, in particular, an elongate sample input opening with a connected elongate sample input chamber and an integrated rod passage recess, which enables a particularly simple and safe input of a sampling device. The sample input chamber 110 for the input of a liquid sample, on the other hand, has in particular a circular sample input opening, which is designed only by way of example for the input of a liquid sample by means of pipetting. In this exemplary embodiment, the carrier device 100 can be combined with two different covering elements or with a covering device and a further covering device, as shown in the following FIGS. 2A and 2B (see FIGS. 3 and 4). For this purpose, the carrier device 100 has combination elements 130, 131, 132 on, which allow a combination of the carrier device 100 with either the covering device or the further covering device while producing a mechanically coherent connection. The first combination element 130 is, purely by way of example, a circular attachment with a conically tapering recess, which in this exemplary embodiment is shaped to accommodate a centering pin. The second combination element 131 and the third combination element 132 are formed as latching hooks, merely by way of example.

FIG. 2A shows a schematic top view representation of a covering device 200 according to an embodiment. The covering device 200 can be combined with a carrier device, as described in the previous figure, and is designed to partially cover the carrier device and completely cover the sample input chamber of the carrier device. In this advantageous exemplary embodiment, the cover device 200 is characterized in particular by a movable sample entry flap 205 with an integrated closure element 210 for the reversible closure of the further sample entry chamber. The closure element 210 can only be used by a user by means of a press fit to close a sample input opening of the further sample input chamber. In order to irreversibly close the sample entry flap 205, the closure element 210 in this exemplary embodiment comprises a closure element 212, which is formed as a latching hook, merely by way of example. By means of the closing element 212, an irreversible closing of the sample input chamber by a user is made possible, merely by way of example. Furthermore, in this exemplary embodiment, the covering device 200 includes further information for the user. Thus, a first information element 215 is arranged on the covering device 200, merely by way of example, which in this exemplary embodiment provides information in the form of characters relating to the type of test that can be carried out in a lab-on-chip cartridge. In addition, the covering device 200 has a second information element 220 which specifies the sample type that is compatible with the respective lab-on-chip cartridge. In this exemplary embodiment, the second information element 220 specifies the exact type of sampling device, with the information provided to the user being partly in the form of an icon in this exemplary embodiment is designed. Thus, in connection with the second information element 220 , a sampling device (swab or flocked potter) is shown pictographically on the covering device 200 , merely by way of example. In the particularly advantageous exemplary embodiment shown here, the covering device 200 also includes a data matrix code 225, which can only be detected by an analysis device as an example, in order to transmit to it the sequence required for processing the respective lab-on-chip cartridge. In another exemplary embodiment, the covering device can additionally or alternatively have information that can be read using RFID.

FIG. 2B shows a schematic top view representation of a further covering device 230 according to an embodiment. The further covering device 230 can be combined with a carrier device, as was described in the preceding FIG. 1, and is designed to partially cover the carrier device and completely cover the further sample input chamber of the carrier device. In this advantageous exemplary embodiment, the further cover device 230 is distinguished by a further movable sample entry flap 235 for the reversible closing of the sample entry chamber of the carrier device. Furthermore, the further covering device 230 comprises, merely by way of example, a further first information element 240 which, merely by way of example, provides information regarding the type of test of the lab-on-chip cartridge. In addition, the further covering device 230 has a further second information element 245 which, in this exemplary embodiment, specifies the sample type which is compatible with the lab-on-chip cartridge. In this exemplary embodiment, the further second information element 245 includes specifications relating to the type of sample medium and its quantity and is designed in part in the form of a pictogram merely by way of example. In connection with the further second information element 245, for example, a pipette is shown pictorially on the further covering device 230, which symbolizes the introduction of a liquid sample by means of a pipette. In addition, the further covering device 230 in this exemplary embodiment has a further data matrix code 250, which can only be detected by an analysis device as an example, in order to transmit to it the sequence required for processing the respective lab-on-chip cartridge. In this exemplary embodiment, the covering device 200 and the further covering device 230 have the same external dimensions and are designed to be complementary to one another: In the case of the covering device 200, a sample can be input into the further sample input chamber via the movable sample input flap 205, while no input into the sample input chamber is possible. Conversely, in the case of the additional cover device 230, a sample can be input into the sample input chamber via the additional movable sample input flap 235, while no input into the additional sample input chamber is possible.

In this way, by using an individualized cover element, it can be prevented in an advantageous manner that the user incorrectly inserts a sample into the wrong one of the two sample input chambers. The two sample entry flaps 205, 235 of the cover devices 200, 230 are also advantageously optimized for the respective sample entry chamber: In this advantageous embodiment, the sample entry flap 205 has, for example, an optical window through which the position of a sampling device within the sample entry chamber can be viewed by a user is detectable.

FIG. 3 shows a schematic plan view representation of a microfluidic device 300 according to an embodiment. The microfluidic device 300 is designed to analyze sample material. For this purpose, the device 300 comprises a carrier device 100, which is designed with a microfluidic network 105 for processing the sample material, and with a sample input chamber 110 arranged on the carrier device 100 and a further sample input chamber 120. The carrier device 100 shown here corresponds to or is similar to the previous one Figure 1 described carrier device. The sample input chamber 110 is only designed as an example to input a liquid sample, for example an aqueous solution, for example obtained from a biological substance, for example of human origin, such as a body fluid, a smear, a secretion, sputum, a tissue sample or a device with attached sample material . the other Sample entry chamber 120 is designed in this embodiment for entering a swab sample. The additional sample input chamber 120 is designed purely by way of example to receive a sampling device with attached sample material, for example a so-called swab or flocked swab with an attached swab sample, for example a nose and throat swab (nasopharynx swab), a wound swab or a vaginal swab. Smear. The device 300 also includes a covering device 200 which is designed to partially cover the carrier device 100 . The covering device 200 shown here corresponds to or is similar to the covering device shown in the previous FIG. 2A. In this case, the covering device 200 is designed to cover the sample input chamber 110, which is correspondingly only indicated by dashed lines in the illustration shown here. The microfluidic device 300, which can also be referred to as a lab-on-chip cartridge, results from the combination of the carrier device 100 with the cover device 200. In another exemplary embodiment, as shown in the following FIG Device can also be formed from the combination of the carrier device with the further covering device. In both exemplary embodiments, an individualized sample input is implemented in an advantageous manner. Depending on the type of sample used, the reagents required for processing the sample substance within the lab-on-chip cartridge may differ. In this embodiment, the microfluidic device 300 has overall lateral dimensions of 118 x 78 mm ² and is fabricated using polycarbonate (PC) and thermoplastic polyurethane (TPU). In another embodiment, the device can have overall lateral dimensions of, for example, 50 x 20 mm ² to 300 x 200 mm ² , preferably 75 x 25 mm ² to 200 x 120 mm ² , and can also be realized using other polymers, for example such as polystyrene (PS), styrene-acrylonitrile copolymer (SAN), polypropylene (PP), polyethylene (PE), cycloolefin copolymer (COP, COC), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS) or by thermoplastic elastomers (TPE ) such as styrene block copolymer (TPS), for example manufactured by series production processes such as injection molding, thermoforming, stamping or laser transmission welding. FIG. 4 shows a schematic plan view representation of a microfluidic device 300 according to an embodiment. The device 300 shown here corresponds to or is similar to the device shown in the previous FIG. 3, with the difference that in this exemplary embodiment the microfluidic device 300 includes a further covering device 230 in addition to the carrier device 100 instead of the covering device. The additional cover device 230 is designed to partially cover the carrier device 100 and is designed to cover the additional sample input chamber 120 . Correspondingly, an input of sample material into the sample input chamber 110 is made possible in this exemplary embodiment. In another exemplary embodiment, the microfluidic device can also include a cover device, which can enable sample material to be input both into the sample input chamber and into the further sample input chamber. In such an embodiment, compared to a lab-on-chip cartridge with only one accessible sample input chamber, the number of handling steps a user needs to be increased, which are required to input a sample into exactly one of the two sample input chambers, since both sample input chambers should be sealed prior to inserting the lab-on-chip cartridge into an analyzer. Accordingly, two handling steps may be required by the user: either closing both sample input chambers after the sample substance has been entered into one of the two sample input chambers or, if the sample input chambers are initially closed, opening and closing exactly one of the two sample input chambers. On the other hand, there is also the risk that the user enters the sample substance into the wrong one of the two sample input chambers, which is intended for the input of a different sample type. This can mean, for example, that after the sample has been put into the lab-on-chip cartridge, the sample cannot be analyzed correctly in the analysis device. Furthermore, in a device with two accessible sample input chambers, depending on the type of sample, different reagents may also be necessary in order to process the sample substance that is input in the lab-on-chip cartridge. Unless in the lab-on-chip cartridge in a costly manner If reagents for both types of samples are stored in advance, a lab-on-chip cartridge may only be able to analyze a specific, specified type of sample. If, on the other hand, an incorrect sample type is entered in a lab-on-chip cartridge that is not intended for this purpose and does not contain the reagents required for the sample type, this can mean that the sample entered cannot be analyzed, even if it is e.g. entered into the correct sample input chamber of the lab-on-chip cartridge.

FIG. 5 shows a schematic top view representation of a storage container 500 according to an embodiment. The storage container 500, which can also be referred to as a reagent bar, is designed in this exemplary embodiment to provide reagents to the microfluidic device, as was described in the previous FIGS. 3 and 4. In the advantageous exemplary embodiment shown here, up to three different liquid reagents are enclosed in a reagent bar in three foil-sealed liquid reagent storage chambers 505, 510, 515. In this exemplary embodiment, the reservoir 500 contains in particular a combination of liquid reagents which are provided for processing a sampling device inserted into a lab-on-chip cartridge. In another embodiment, however, the reagent bar can contain in particular a collection of liquid reagents which are intended for processing a liquid sample entered into a lab-on-chip cartridge, for example aqueous solutions, for example buffer solutions, or mineral oils, silicone oils or fluorinated hydrocarbons . In this exemplary embodiment, the reservoir 500 has dimensions which are compatible with the support device described in FIG. 1 above. So that the storage container 500 shown here can be distinguished from another exemplary embodiment, it has an individual information unit 520, which in this exemplary embodiment is in the form of a data matrix code. The information unit 520 is designed merely by way of example to provide information about the liquid reagents present in the reagent bar. In another exemplary embodiment, the information unit can additionally or alternatively, a batch designation and/or information on filling the reagents can also be provided. The information can be retrieved, for example, during the manufacture of the lab-on-chip cartridge in order to ensure that the carrier device is fitted with the correct liquid reagents.

6 shows a schematic plan view of an embodiment of a carrier device 100 with a storage container 500. The carrier device 100 shown here corresponds or is similar to the carrier device described in the previous FIGS. In this exemplary embodiment, the carrier device 100 has a liquid reagent holder 600 which is designed for combination with individual liquid reagents. In the representation shown here, a storage container 500 is arranged in the liquid reagent receptacle 600 purely by way of example. The storage container 500 shown here corresponds to or is similar to the storage container described in FIG. 5 above. In this exemplary embodiment, the carrier device 100 is individualized for the analysis of a swab sample connected to a sampling device through the combination with a reagent block. In another embodiment, the carrier device can be individualized with a variant of the storage container for the analysis of a liquid sample. In a further exemplary embodiment, the carrier device can have a standardized liquid reagent holder, which can be provided, for example, for receiving a plurality of at least two different reagent bars. In this way, the number of liquid reagents that are used within a lab-on-chip cartridge can be increased, for example to be able to carry out more complex test sequences in the lab-on-chip cartridge. In this exemplary embodiment, the carrier device 100 also has an evaluation chamber 605 for evaluating sample material, the evaluation chamber 605 being fluidically connected to the sample input chamber 110 and the further sample input chamber 120, merely by way of example.

FIG. 7 shows a flowchart of a method 700 for manufacturing a microfluidic device according to an embodiment. The procedure 700 includes a step 705 of providing the carrier device and the cover device, which is designed to cover the sample input chamber. Merely by way of example, the step 705 of providing in this exemplary embodiment has a plurality of sub-steps. In sub-step 706 of arranging, at least two semi-finished products for producing a carrier device are arranged on a workpiece carrier, merely by way of example. The semi-finished products are only flat in some areas, for example, and have the same or similar lateral dimensions. In this advantageous exemplary embodiment, the workpiece carriers include adjustment pins which engage in adjustment through-holes in the semi-finished products in order to achieve a defined positioning of the semi-finished products on the workpiece carrier and a defined relative positioning of the at least two semi-finished products to one another. In this exemplary embodiment, the latter serves to prepare a subsequent sub-step 707 of disposition. In sub-step 707 of joining, at least two semi-finished products arranged on a workpiece carrier are joined together to form the carrier device. The joining of the at least two semi-finished products is carried out only by way of example using a series production technology such as laser transmission welding. The two semi-finished products are pressed together in this exemplary embodiment in order to achieve consistently good heat conduction between the at least two semi-finished products during the welding process. In the sub-step 708 of equipping, in this exemplary embodiment a semi-finished product or an assembly consisting of a plurality of semi-finished products for producing the carrier device is fitted with at least one further part. The other part is merely an example of a reagent bar, which is inserted into a liquid reagent receptacle provided for this purpose. In another embodiment, it can be a reaction bead, i.e. a freeze-dried or lyophilized solid reagent, which can be introduced into a recess provided for this purpose in a semi-finished product or an assembly of a plurality of semi-finished products to form the carrier device. In a further exemplary embodiment, it can be, for example, an array support element such as a hybridization array or a microcavity array which is used to carry out detection reactions in the microfluidic Device can be used. The array carrier element can, for example, be glued into the semi-finished product or the subassembly made up of a plurality of semi-finished products to form the carrier device. In this exemplary embodiment, the sub-step 708 of loading is followed, by way of example only, by a sub-step 709 of repeating. In this sub-step, the sub-step 706 of arranging, the sub-step 707 of having and the sub-step 708 of equipping are repeated merely by way of example. A multilayer microfluidic device with inserted parts such as reagent bars and solid reagents is formed merely by way of example by multiple execution of the sub-steps 706 of arranging, 707 of having and 708 of equipping. In another exemplary embodiment, only two or only one of the sub-steps can also be repeated and/or the order in which the sub-steps are carried out can be interchanged. For example, a sub-step of assembly can be followed by a sub-step of arrangement and a sub-step of assembly in order to place the parts that may have been introduced in the sub-step of assembly into a semi-finished product or an assembly consisting of a plurality of semi-finished products for the production of a carrier device, within the enclose the resulting microfluidic device or to provide it with an enclosure.

Step 705 of providing is followed by a step 710 of covering at least part of the carrier device with the covering device, with the sample input chamber being covered by the covering device. In this exemplary embodiment, the covering device is applied by snapping in, for example only. In another embodiment, the covering can also be done by plugging it on. Furthermore, the method 700 comprises a step 715 of providing a further example of the carrier device and the further covering device, which is designed to cover the further sample input chamber of the further example of the carrier device. In this exemplary embodiment, the carrier device is only provided by way of example congruently with the carrier device provided in step 705 of providing, with corresponding sub-steps. The step 715 of providing is followed by a step 720 of covering at least part of the further copy of the Carrier device with the further cover device, wherein the further sample input chamber of the further copy of the carrier device is covered by the further cover device. In further exemplary embodiments of the method 700 for producing a microfluidic device with individualized sample input, individual steps or sub-steps can be omitted or carried out repeatedly and/or the sequence can be interchanged with other steps.

FIG. 8 shows a flow chart of a method 700 for manufacturing a microfluidic device according to an embodiment. Method 700 corresponds to or is similar to the method described in the preceding FIG. 7, with the difference that step 705 of providing the carrier device and the covering device takes place in parallel with step 715 of providing the carrier device and the further device. In other words, carrier devices of the same design are provided, which can be combined both with a covering device and with a further covering device. In this exemplary embodiment, steps 705 of providing and 715 of providing are also followed by step 710 of covering part of the carrier device with the covering device, with the sample input chamber being covered by the covering device, and step 720 of covering at least part of the Carrier device with the further cover device, the further sample input chamber being covered by the further cover device. In addition to providing a suitable sample input functionality of a lab-on-chip cartridge, the lab-on-chip cartridge should also be particularly easy to manufacture. In this context, a separate production of at least two different cartridge variants, each with a sample input chamber specialized for a specific sample type, appears to be disadvantageous, since the resulting variety of variants of the individual components for forming the lab-on-chip cartridge is associated with considerable additional effort.

One possible solution is therefore, for example, to provide exactly one lab-on-chip cartridge or a carrier device with a plurality of at least two separate sample input chambers at least two separate sample input chambers of this lab-on-chip cartridge or carrier device are each optimized for at least one type of sample.

9 shows a flowchart of a method 900 for using a microfluidic device according to an embodiment. The method 900 comprises, purely by way of example, an input step 905 in which a sample substance of a specific sample type is input into the microfluidic device. In this exemplary embodiment, in this step 905 of inputting, a sampling device with connected sample material is input, that is to say a swab sample is input. In other exemplary embodiments, depending on the device and the covering device combined with the carrier device of the device, either a sampling device with attached sample material can be input or a liquid sample can be input into the device. In an advantageous embodiment of the device with individualized sample input, the sample type compatible with the respective lab-on-chip cartridge is communicated to a user iconographically by the cover element. The method 900 also includes a step 910 of receiving the device in an analysis device. In this step, which can also be referred to as the introduction step, the microfluidic device is introduced into an analysis device, which can also be referred to as an analysis device. In this exemplary embodiment, the step 910 of receiving is followed by a step 915 of processing sample material entered into the sample input chamber. In another exemplary embodiment, sample material entered into the further sample input chamber can also be processed in the processing step. In this case, the device is processed in the analysis device, for example in order to process a sample substance therein. In an advantageous exemplary embodiment, the processing step can also have a detection sub-step, in which the exact type of the device introduced in the insertion step can be detected. The detection can take place, for example, via a data matrix code applied to a covering device or by reading out using RFID. Depending on the result of the detection, for example, a special flow log for Process brought-in device is called and the brought-in device can be processed. Merely as an example, the method 900 in this exemplary embodiment includes a further step 920 of evaluation, in which sample material introduced from the sample input chamber into an evaluation chamber, merely as an example, is evaluated. In another exemplary embodiment, sample material introduced into an evaluation chamber from the further sample input chamber can be evaluated additionally or alternatively in the evaluation step. In addition, in this exemplary embodiment, step 920 of evaluation is followed by a further step 925 of output, in which the device is output from the analysis device. Optionally, an analysis result can also be output in the output step.

FIG. 10 shows a schematic representation of an exemplary embodiment of an analysis device 1000 for accommodating a microfluidic device. The analysis device 1000 is designed, merely by way of example, to accommodate a microfluidic device, as was described in the previous FIGS. 3 and 4, by means of an input opening 1005, in order to carry out analysis processes within the device. In this case, the analysis device 1000 in this exemplary embodiment comprises a control unit 1010 which is designed to control steps of the method described in the previous FIG. 9 in relation to the device.

If an embodiment includes an "and/or" link between a first feature and a second feature, this should be read in such a way that the embodiment according to one embodiment includes both the first feature and the second feature and according to a further embodiment either only that having the first feature or only the second feature.

Claims

- 27 - Claims

1. A microfluidic device (300) for analyzing sample material, the device (300) having the following features: a carrier device (100) which is formed with a microfluidic network (105) for processing the sample material; at least one sample input chamber (110) arranged on the carrier device (100) and at least one further sample input chamber (120) arranged on the carrier device (100); and at least one cover device (200) to at least partially cover the carrier device (100), the cover device (200) being designed to cover the sample input chamber (110) or at least one further cover device (230) to cover the carrier device (100) at least cover partially, wherein the further cover device (230) is designed to cover the further sample input chamber (120).

2. Microfluidic device (300) according to claim 1, wherein the sample input chamber (110) is designed to input a liquid sample and/or wherein the further sample input chamber (120) is designed to input a swab sample.

3. Microfluidic device (300) according to one of the preceding claims, wherein the covering device (200) and the further covering device (230) have the same external dimensions within a tolerance range. Microfluidic device (300) according to one of the preceding claims, having at least one combination element (130, 131, 132) for mechanically connecting the carrier device (100) to the covering device (200) and/or the further covering device (230). Microfluidic device (300) according to one of the preceding claims, wherein the cover device (200) and/or the further cover device (230) comprises a closure element (210) for reversibly closing the sample input chamber (110) and/or the further sample input chamber (120). Microfluidic device (300) according to claim 5, wherein the cover device (200) has at least one closure element (212) arranged on the closure element (210) for irreversibly closing the closure element (210). Microfluidic device (300) according to one of the preceding claims, wherein the covering device (200) and/or the further covering device (230) has at least one information element (215, 220) for providing device-specific information. Microfluidic device (300) according to one of the preceding claims, with a reservoir (500) for providing reagents to the device (300), wherein the reservoir (500) has at least one information unit (520) for providing at least one reagent-specific information. Microfluidic device (300) according to one of the preceding claims, with an evaluation chamber (605) for evaluating sample material, wherein the evaluation chamber (605) is fluidically connected or connectable to the sample input chamber (110) and the further sample input chamber (120). Microfluidic system with a microfluidic device (300) according to one of Claims 1 to 9 with the covering device (200) and the further covering device (230). Method (700) for producing a microfluidic device (300) according to one of the preceding claims, wherein the method (700) comprises the following steps (705, 710, 715, 720):

providing (705) the carrier device (100) and the cover device (200) which is designed to cover the sample input chamber (110);

Covering (710) at least part of the carrier device (100) with the covering device (200), the sample input chamber (110) being covered by the covering device (200);

Providing (715) a further copy of the carrier device (100) and the further cover device (230), which is designed to cover the further sample input chamber (120) of the further copy of the carrier device (100) and

Covering (720) at least part of the additional copy of the carrier device (100) with the additional cover device (230), the additional sample input chamber (120) of the additional copy of the carrier device (100) being covered by the additional cover device (230). Method (900) for using a microfluidic device (300) according to any one of claims 1 to 9, wherein the method (900) comprises the following steps (910, 915):

incorporating (910) the device (300) into an analyzer (1000); and Processing (915) of sample material introduced into the sample input chamber (110) or into the further sample input chamber (120), in particular an evaluation step (920) being provided in which from the sample input chamber (110) and/or from the further sample input chamber ( 120) sample material introduced into an evaluation chamber (605) is evaluated. Control unit (1010) that is set up to execute and/or control the steps (705, 710, 715, 720; 910, 915) of one of the methods (700; 900) according to one of the preceding claims 11 or 12 in corresponding units. Computer program set up to execute and/or control the steps (705, 710, 715, 720; 910, 915) of one of the methods (700; 900) according to one of the preceding claims 11 or 12. Machine-readable storage medium on which the computer program according to claim 14 is stored.