Microfluidic device for analyzing sample material and method for operating microfluidic device

Abstract

The invention relates to a microfluidic device (100) for analyzing a sample material, the device (100) having a microfluidic network (105), the network (105) comprising a first sub-network (110) for cleaning the sample material. In the first sub-network (110), a first microfluidic pump chamber (151) and a second microfluidic pump chamber (152) are connected in series with a functional module (270) for filtering the sample material.

Description

Technical Field

[0001] The invention relates to a microfluidic device for analyzing a sample material and a method for operating a microfluidic device according to the generic terms of the independent claims. A computer program is also a subject of the invention. Background Art

[0002] Microfluidic analysis systems, so-called labs on a chip (Lab-on-Chips, LoCs for short), allow automated, reliable, rapid, compact and cost-effective processing of patient samples for medical diagnosis. By combining a plurality of operations for the controlled processing of fluids, complex molecular diagnostic test processes can be carried out in a Lab-on-Chip cartridge, which can also be referred to as a microfluidic analysis device. Lab-on-Chip cartridges can be produced cost-effectively from polymers, for example, using mass production methods such as injection molding, stamping or laser transmission welding. The processing of the Lab-on-Chip cartridge takes place in the analytical device to which it belongs. Different types of microfluidic analysis systems are known.

[0003] DE 10 2021 203 638 A1 discloses a corresponding microfluidic device for analyzing a sample material, wherein the device comprises a first subnetwork for purifying the sample material and a second subnetwork for amplifying the sample material, which is connected to the first subnetwork via a connecting channel. Summary of the invention

[0004] Against this background, the solution presented here provides a microfluidic device for analyzing a sample material and a method for operating a microfluidic device according to the independent claims, furthermore a control device using this method and finally a corresponding computer program. Advantageous modifications and improvements of the device described in the independent claim can be achieved by the measures mentioned in the dependent claims.

[0005] In general, pressure-based microfluidic analysis devices have multiple active microfluidic elements, such as valves and pump chambers, which are connected to each other in a suitable network consisting of microfluidic channels. The pneumatic control of active microfluidic elements is realized by the pneumatic microchannels inside the microfluidic device, which can apply overpressure or underpressure through the interface of the microfluidic analysis device that is as compact as possible and leads to the analytical device (which can also be used as a processing unit) so as to cause the actuation of the microfluidic element by the corresponding deflection of the elastic diaphragm. Therefore, when designing such a microfluidic analysis device, the particularly advantageous arrangement structure of the element and the design of the microfluidic network are considered in particular, so that the preset application range can be covered by the microfluidic device in a particularly advantageous manner. The microfluidic device proposed here provides a particularly advantageous design of a microfluidic network, which has an active, pneumatically controllable element for processing a sample liquid. Here, it is advantageously possible to minimize the consumption of the reagent required for performing the test flow, wherein a particularly high reliability in microfluid processing can be achieved at the same time.

[0006] A microfluidic device for analyzing sample material is proposed, wherein the device has a microfluidic network, wherein the network includes a first subnetwork for extracting and thereby purifying the sample material, and optionally includes a second subnetwork for replicating and thereby amplifying the sample material, the second subnetwork being connected to the first subnetwork via a connecting channel.

[0007] If the microfluidic device comprises a second subnetwork, the first subnetwork and the second subnetwork can optionally be arranged in a linear topology. Furthermore, the subnetworks can be separated from one another.

[0008] The first subnetwork includes a first functional module for providing a liquid reagent, a second functional module for inputting a sample substance, a third functional module for filtering the sample material, a fourth functional module for storing a liquid, and a first microfluidic pump chamber and a second microfluidic pump chamber for establishing fluid transport. According to a special design, the second functional module and the fourth functional module can also be constructed as a common functional module. The first microfluidic pump chamber and the second microfluidic pump chamber are connected in series with the third functional module for filtering the sample material.

[0009] The optional second subnetwork comprises a first functional module for amplifying the sample material and optionally a second functional module for solubilizing at least one amplification reaction bead.

[0010] The microfluidic device can be, for example, a chip lab cartridge, which is a component of a pressure-based microfluidic analysis system. Here, the liquid transport inside the microfluidic analysis device can be realized by applying a mostly pneumatic pressure. The sample material can be, for example, a sample liquid, which can be derived from a sample substance input into the microfluidic device and can be processed inside the microfluidic device. Here, the sample substance can be understood as a sample, such as a liquid sample or a smear sample, that can be input into the cartridge. In contrast, the sample material can also be, in particular, only a component of the sample substance, which is obtained from the sample substance, for example, by extraction. This sample liquid can be, for example, an aqueous solution, which is obtained from biological substances, such as biological substances, such as body fluids, smears, secretions, saliva, tissue samples, or devices attached with sample materials. In the sample liquid, there can be, for example, species related to medicine, clinic, diagnosis or treatment, such as bacteria, viruses, cells, circulating tumor cells, cell-free DNA, proteins or other biomarkers or components especially from the object mentioned. The sample liquid can be, for example, a master mix or a component thereof, which is used, for example, to perform at least one amplification reaction in a microfluidic analysis device, for example, for DNA detection at a molecular level, such as an isothermal amplification reaction or a polymerase chain reaction. Here, in the device, for example, the sample material can be first extracted from the sample material input, such as a liquid sample or a smear sample. That is, the sample material can be purified so that the components of the sample material can be amplified subsequently. Purification is particularly advantageous because the original sample material may contain components that have an adverse effect on the amplification reaction, i.e., so-called inhibitors. In the subsequent amplification reaction, only the components of the original sample material, such as a specific DNA base sequence, can be amplified, i.e., replicated. By locally applying an overpressure or underpressure, for example, an elastic diaphragm as a component of a microfluidic device can be purposefully deflected in a recess in the microfluidic device, so that in this way a liquid is sucked into the recess or squeezed out of the recess. Here, the microfluidic, liquid-guided region (on the one hand) and the pneumatic region of the device can be separated from the external environment (on the other hand) by the elastic diaphragm. Depending on the size of the recess in the liquid-conducting region and the displacement associated therewith, when the diaphragm is deflected into this region, for example, a microfluidic pump chamber with a large displacement can be present for the flow in the main generating device, or a microfluidic valve with a small displacement can be present for the flow in the main control device. By means of a combination of at least three microfluidic pump chambers and additional or alternative valves, a directional flow can be generated in the microfluidic device by continuously actuating the elements. For example, a pump chamber can be combined with two surrounding valves, i.e. an inlet valve and an outlet valve, in order to achieve a directional liquid transport.Furthermore, for example, three similar elements with similar displacements can also be combined with one another in order to bring about a peristaltic fluid transport by means of a row-by-row, sequential actuation.

[0011] For example, the functional module of the first subnetwork can be used continuously for purifying or extracting sample material. Here, the first functional module can provide a liquid reagent, in which the sample material can be dissolved and transported in the device as an additional solution or an alternative. The sample material can be input into the second functional module in the form of a sample liquid or a smear sample, and can be dissolved by a carrier element, such as a sampling device, when necessary. When using the third functional module, for example, a specific species can be filtered out from the sample material so that only the part to be analyzed of the sample material can be transported in the following process. In the fourth functional module, for example, liquids produced during the purification of the sample material can be stored or stored intermediately. Here, liquid transportation can be established between different functional modules and as an additional solution or an alternative between subnetworks by means of a pump module. Therefore, for example, after the sample material can be purified in the functional module of the first subnetwork, the fluid accumulated with the sample material can be transported to the second subnetwork through a connecting channel from the first subnetwork. Here, the sample material can be replicated or amplified in the first functional module, and for example, so-called amplification reaction beads can be provided in the second functional module. Thus, the number of flushing steps required for testing the process in the inside of the microfluidic device can be advantageously reduced. In this way, the time required for carrying out the test process can be shortened.

[0012] According to another embodiment, the fourth functional module of the first subnetwork and the first functional module of the second subnetwork can be fluidically connected via a connecting channel. For example, liquid generated when purifying the sample material can be stored in the fourth functional module of the first subnetwork. When using the connecting channel, the liquid with the sample material can be transported to the first functional module of the second subnetwork, and the sample material can be subsequently amplified. Advantageously, the separation of the individual functional modules and the subnetworks from each other can be simplified by the unique connection of the two functional modules and can prevent lateral contamination between different process steps, that is, can prevent the undesirable mixing of different liquid solutions used during the test process.

[0013] At this, the device proposed here advantageously has different functional delimitations that can be provided by the microfluidic device in the form of a subnetwork that can be separated by microfluids. Here, "subnetwork" can be understood as a plurality of interconnected microfluidic elements. As mentioned above, a microfluidic element can be a passive element, such as a cavity, or an actuable element, such as a pump chamber, a pump or a valve. The subnetwork preferably includes at least two, preferably more than two microfluidic elements that are fluidically connected to each other. Two subnetworks that can be separated from each other refer in particular to that the two subnetworks are arranged in two regions that are separated from each other in position, and can be separated from each other by plane segmentation in a preferred design. As an alternative or supplementary solution, two subnetworks that can be separated from each other can be understood as that the two subnetworks are connected to each other by one or more channels, preferably only by one channel, wherein the channel can preferably be separated from each other by fluid by at least one fluid separation element, such as a valve.

[0014] Based on the separable subnetworks, it is advantageously possible to implement multiple control of microfluidic elements that can be assigned to different subnetworks. In addition, separate execution of purification and amplification in separate subnetworks can reduce the number of rinsing steps and prevent undesired microfluidic crosstalk between different process steps.

[0015] By arranging the first subnetwork and the second subnetwork in a linear topology, the subnetworks are thus arranged linearly or in a row, which achieves a linear network topology, through which dead volumes that may occur when carrying out a test process within the microfluidic analysis device can be particularly small. In this advantageous manner, the amount of reagents required for carrying out a test process within the microfluidic device can be reduced.

[0016] The functional modules of the first subnetwork and the functional modules of the second subnetwork as a supplement or alternative can be separated from each other in terms of fluid. For example, each functional module can realize a specific task within the purification or analysis process and has a variable number of separate elements, such as valves, pump chambers or storage chambers for this purpose. Here, each functional module can be separated from each other by means of a separation valve, for example. In addition, in a preferred design, at least some of the functional modules in the functional module can be arranged in a linear topological structure. The functional module can be controlled, for example, continuously during the purification and analysis process, so as to, for example, first extract species from the sample material and then detect the species or its components in the separate areas of the proposed microfluidic analysis device. Thus, it is possible to advantageously prevent possible crosstalk, that is, to prevent the undesirable mixing of different liquid solutions that may be produced by the multiple use of a specific area of ​​the microfluidic network. In this way, the efficiency of the chemical reaction carried out in the microfluidic analysis device can be improved and the sensitivity that can be achieved when detecting can be improved.

[0017] The first microfluidic pump chamber and the second microfluidic pump chamber can be used to establish a fluid transport through a third functional module for filtering the sample material. In addition, the two pump chambers can be used to establish a fluid transport through the first subnetwork and optionally other functional modules of the second subnetwork and / or a fluid transport from the first subnetwork to the second subnetwork. According to one embodiment, the first subnetwork includes no other pump chambers or pump mechanisms in addition to the first microfluidic pump chamber and the second microfluidic pump chamber.

[0018] By connecting the two pump chambers in series with the third functional module for filtering the sample material, the two pump chambers can be used together in order to generate a pressure difference between the connections of the third functional module.

[0019] For this purpose, the device can have a control interface for applying a first pressure to the first microfluidic pump chamber and a control interface for applying a second pressure to the second microfluidic pump chamber. In this case, the first pressure can cause squeezing of the first microfluidic pump chamber and the second pressure can cause suction with the second microfluidic pump chamber. By combining squeezing and suction, a large pressure difference can be caused on the third functional module. For example, the first pressure can be an overpressure and the second pressure can be an underpressure, respectively, relative to the ambient pressure.

[0020] According to one embodiment, the first interface of the first microfluidic pump chamber can be connected to a first functional module for providing a liquid reagent and a second functional module for inputting a sample material. The second interface of the first microfluidic pump chamber can be connected to a first interface of a third functional module for filtering the sample material. The first interface of the second microfluidic pump chamber can be connected to a second functional module for inputting a sample material. The second interface of the second microfluidic pump chamber can be connected to a second interface of the third functional module for filtering the sample material. According to an embodiment, the corresponding interfaces can be connected directly, i.e., without other intermediate connecting elements, or, for example, detachably, i.e., for example, connected by at least one intermediately connected microfluidic valve.

[0021] The third functional module can include a filter element, which can be detachably connected to the first interface of the third functional module and detachably connected to the second interface of the third functional module. In addition, the third functional module can include at least one microfluidic valve, which is connected between the first interface and the second interface of the third functional module. Thus, the filter element can be bypassed. The filter element can be shaped as a corresponding known filter and can realize the extraction of components from the liquid.

[0022] The second functional module can include a sample input chamber for inputting a sample substance. Here, the sample input chamber can be detachably connected to the first interface of the second functional module and detachably connected to the second interface of the second functional module. The first interface of the first microfluidic pump chamber can be connected to the first interface of the second functional module and the first interface of the second microfluidic pump chamber can be connected to the second interface of the second functional module. Advantageously, the pump chamber can also be used to transport the sample substance input into the sample input chamber through the first sub-network.

[0023] According to one embodiment, the device can have a common control interface for applying pressure, wherein the common control interface can be connected to the elements of the functional module of the first sub-network through a first control channel and connected to the elements of the functional module of the second sub-network through a second control channel. The element can be, for example, a valve or pump chamber of the device or other microfluidic element. For example, an overpressure or underpressure can be applied to a common control interface that can also be called a port or a control port in order to control the elements of the functional module of the sub-network. In this advantageous manner, multiple active elements belonging to different functional modules can be connected through a common control channel. In other words, multiple detections can be achieved during control. By multiple detections when controlling active microfluidic elements, the number of control ports required for controlling a preset microfluidic network can be advantageously reduced. In this way, the cost generated for an analytical device, that is, in particular a processing unit, can be reduced. In addition, a microfluidic network with an increased functional range can be realized with a preset number of control ports when controlling active microfluidic elements through multiple detections. In this way, the scope of application defined by such a microfluidic analysis device can be expanded.

[0024] According to another embodiment, the fourth functional module of the first subnetwork can have a first shut-off valve for closing the connecting channel, and as a supplement or alternative, the first functional module of the second subnetwork can have a second shut-off valve for closing the connecting channel. For example, the first shut-off valve can remain closed while the sample material is being processed in the first subnetwork. This has the advantage that the transport fluid with the sample material used in the first subnetwork can be prevented from entering the second subnetwork undesirably and prematurely. After transport to the second subnetwork, both shut-off valves can be opened, and the closing of the second shut-off valve can also advantageously prevent the transport fluid with the sample material from flowing back into the first subnetwork.

[0025] According to another embodiment, the device can include a valve control interface for applying pressure, wherein the first shutoff valve and the second shutoff valve can be controlled by means of the valve control interface. For example, the first shutoff valve and the second shutoff valve can be closed or opened simultaneously by means of the valve control interface in order to allow or prevent the transfer of fluid between the first subnetwork and the second subnetwork of the device. By common control, the number of control elements required for the processing of the device can be advantageously reduced and the cost of the system can thus be reduced.

[0026] According to another embodiment, the fourth functional module of the first subnetwork can be configured to output the sample material. If, for example, only purification and extraction of the sample material are performed in the device, the sample material can be taken out of the microfluidic device again after extraction, without being transported to the second subnetwork. For this purpose, the fourth functional module can, for example, include an output mechanism for outputting the sample material. Thus, the device can be advantageously used variably for different analysis processes.

[0027] According to another embodiment, the first subnetwork can have an additional fourth functional module for storing liquid. In this way, the scope of use of the microfluidic analysis device can be expanded.

[0028] According to another embodiment, the device can include at least one additional control interface for applying pressure, wherein the additional control interface can be connected to an element of a functional module of the first subnetwork or to an element of a functional module of the second subnetwork via an additional control channel. The microfluidic device can, for example, include a plurality of control interfaces, some of which can be configured to control a plurality of elements of different functional modules, while other control interfaces can be used to control specific elements of a functional module. Thus, all elements of a functional module can be advantageously controlled precisely.

[0029] In addition, a method for operating a variant of the microfluidic device proposed above is proposed, wherein the method includes a step of extracting sample material while using a first subnetwork, optionally including a step of transporting the sample material from the first subnetwork to a second subnetwork, and optionally including a step of amplifying the sample material while using the second subnetwork.

[0030] The extraction step includes a filtering substep in which a pressure difference is generated across the third functional module by combining compression of the first microfluidic pump chamber with suction with the second microfluidic pump chamber in order to effect filtering of the sample material.

[0031] According to one embodiment, the step of extracting can have a substep of mixing, and additionally or alternatively a substep of detaching, and additionally or alternatively a substep of lysing, and additionally or alternatively a substep of rinsing. The optional step of transporting can additionally or alternatively have a substep of eluting, and the optional step of amplifying can additionally or alternatively have a substep of dissolving, and additionally or alternatively have a substep of replicating, and additionally or alternatively have a substep of detecting.

[0032] Such a method can be implemented, for example, in software or hardware or in a hybrid form of software and hardware, for example in a control unit.

[0033] In addition, the solution presented here provides a control device, which is designed to execute, control or implement the steps of the variant solution of the method proposed here in corresponding mechanisms. Through this variant embodiment of the invention in the form of a control device, the task on which the invention is based can also be solved quickly and effectively. For example, the control device can be used to apply a pressure suitable for operating the device to the control interface of the microfluidic device.

[0034] For this purpose, the control device can have at least one computing unit for processing signals or data, at least one storage unit for storing signals or data, at least one interface to a sensor or actuator for reading in sensor signals from a sensor or for outputting control signals to an actuator, and / or at least one communication interface for reading in or outputting data embedded in a communication protocol. The computing unit can be, for example, a signal processor, a microcontroller, etc., wherein the storage unit can be a flash memory, an EEPROM, or a magnetic storage unit. The communication interface can be designed for wireless and / or wired reading in or outputting data, wherein a communication interface capable of reading in or outputting wired data can, for example, read in these data from a corresponding data transmission line electrically or optically or output these data to a corresponding data transmission line.

[0035] At present, a control device can be understood as an electrical device that processes sensor signals and outputs control signals and / or data signals accordingly. The control device can have an interface, which can be constructed according to hardware and / or software. In a hardware-based construction scheme, the interface can, for example, be part of a so-called system ASIC, which contains various functions of the control device. However, it is also feasible that the interface is its own integrated circuit or is at least partially composed of discrete components. In a software-based construction scheme, the interface can be a software module, which is, for example, located on a microcontroller in parallel with other software modules.

[0036] Also advantageous is a computer program product or a computer program having a 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 is used, in particular, when the program product or the program is executed on a computer or a device to execute, implement and / or control the steps of the method according to one of the embodiments described above. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] An exemplary embodiment of the solution presented here is shown in the drawings and is explained in more detail in the following description.

[0038] Figure 1 A schematic diagram of a microfluidic device is shown;

[0039] Figure 2 A schematic diagram of a microfluidic device is shown;

[0040] Figure 3 A schematic diagram of a microfluidic device is shown;

[0041] Figure 4 A schematic diagram of a microfluidic device is shown;

[0042] Figure 5 A schematic diagram showing one embodiment of a microfluidic device;

[0043] Figure 6 A schematic diagram showing one embodiment of a microfluidic device;

[0044] Figure 7 A schematic diagram showing one embodiment of a microfluidic device;

[0045] Figure 8 A schematic diagram showing one embodiment of a microfluidic device;

[0046] Fig. 9 shows a perspective top view of an embodiment of a microfluidic device;

[0047] Fig.10 shows a top view of one embodiment of a microfluidic device;

[0048] Fig.11 A partial perspective top view of a microfluidic device according to an embodiment is shown;

[0049] Fig.12 shows a perspective bottom view of a portion of a microfluidic device according to one embodiment;

[0050] Fig.13 A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown;

[0051] Fig.14 A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown;

[0052] Fig.15 A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown;

[0053] Fig.16 A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown; and

[0054] Fig.17 A schematic diagram of an embodiment of an analytical device for receiving a microfluidic device is shown.

[0055] In the following description of advantageous exemplary embodiments of the invention, identical or similar reference numerals are used for similarly acting elements which are illustrated in the various figures, wherein a repeated description of these elements is omitted. DETAILED DESCRIPTION

[0056] Figure 1 A schematic diagram of a microfluidic device 100 is shown. In the present exemplary embodiment, the device 100 has a microfluidic network 105, which optionally has a linear topology. The network 105 is divided into a first subnetwork 110 and an optional second subnetwork 120, wherein the two subnetworks 110, 120 are indicated by dashed lines in the diagram shown here.

[0057] Even though this figure and the following figures show an exemplary embodiment of a microfluidic device 100 having two subnetworks 110 , 120 , the respectively shown microfluidic device can also be implemented with only the first subnetwork 110 , that is, either without including the second subnetwork 120 or with a second subnetwork implemented in another way.

[0058] If the corresponding microfluidic device, e.g. Figure 1 The microfluidic device 100 shown in the figure includes not only the first sub-network 110 but also the second sub-network 120, and the two sub-networks 110 and 120 are connected to each other through a microfluidic connecting channel 125. Optionally, the first sub-network 110 and the second sub-network 120 are arranged in a linear topological structure. However, according to this embodiment and the embodiments shown in the following figures, other types of arrangements of the sub-networks 110 and 120 can also be implemented.

[0059] The first subnetwork 110 and the second subnetwork 120 both include additional microfluidic channels, which are schematically shown as solid lines in the figure shown here, and which connect different microfluidic elements to each other. In the present embodiment, the network 105 of the microfluidic device 100 is particularly characterized by twenty active microfluidic valves 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150. Two valves 144, 145 are only exemplarily arranged on the connecting channel 125 and are configured as a first shut-off valve 144 and a second shut-off valve 145 for closing the connecting channel. Thus, the subnetworks 110, 120 can be separated from each other. The network 105 also includes six active microfluidic pump chambers 151, 152, 153, 154, 155, 156; a passive microfluidic chamber 160; three pre-storage chambers 161, 162, 163 with exhaust openings for pre-storing liquid reagents for a long time and stably; two sample input chambers 167, 168 that can realize sample input; a filter element 170 that can realize the extraction of components from the liquid; a liquid storage chamber 180 for receiving liquid after processing in the microfluidic network 105 and four exhaust devices 191, 192, 193, 194 for exhausting the microfluidic network. In this embodiment, a total of twenty-six active microfluidic elements can be controlled by pneumatic control channels, as shown by reference symbols through lines perpendicular to the microfluidic channel branches. The arrangement structure and connection of the mentioned elements form a microfluidic network 105, which only has a linear topological structure by way of example.

[0060] Here, the microfluidic network 105 of the microfluidic device 100 consists of a first subnetwork 110 and a second subnetwork 120, wherein the first subnetwork is configured to purify the sample material and the second subnetwork is configured to amplify the sample material. The two subnetworks 110, 120 are fluidically connected to each other via a microfluidic connection channel 125. Thus, microfluidic processing can be performed continuously, i.e. sequentially, within the two subnetworks 110, 120 within the framework of executing the test process. Accordingly, the combination formed by the active microfluidic elements respectively arranged in different subnetworks 110, 120 can be controlled by a common control channel when necessary.

[0061] Figure 2The schematic diagram of microfluidic device 100 is shown. The device 100 shown here corresponds to or is similar to the device described in the previous figure and includes a microfluidic network 105, which is divided into a first subnetwork 110 and a second subnetwork 120. In the present embodiment, the microfluidic element of network 105 is arranged in a plurality of functional modules that can be separated from each other within subnetworks 110, 120, wherein each functional module is indicated by the rectangular frame formed by the dot-dash line in the illustration shown here. In detail, in the present embodiment, the subnetwork 110 for purifying sample material includes a pump module 230, which is used to transport fluid and the sample material dissolved therein in the network 105 or between different functional modules. For this reason, the pump module only exemplarily includes two active microfluidic pump chambers 151, 152 and a microfluid valve 136. In addition, the first subnetwork 110 has a first functional module 250 for providing a liquid reagent. In this first functional module, only three pre-storage chambers 161, 162, 163 for pre-storing liquid reagents stably for a long time are exemplarily arranged. Liquid reagent is only exemplarily aqueous solution, for example, for processing the buffer solution of sample material or its component. In another embodiment, mineral oil, silicone oil or fluorinated hydrocarbon can also be stored in the pre-storage chamber. In the present embodiment, each pre-storage chamber 161,162,163 is connected with microfluid valve 131,132,133 fluid respectively, and the microfluid valve is connected with each other fluidly and with the second channel interface 257 fluid by the first channel interface 255 again. By the closing of valve 131,132,133, the first functional module 250 can be separated from the remaining microfluid network 105. In the present embodiment, the first functional module 250 is connected with the pump module 230, the second functional module 261 for inputting sample material and only exemplarily with the additional second functional module 262 for inputting sample material via the second channel interface 257. Here, the second functional module 261 comprises the sample input chamber 167 with exhaust device 191. The sample input chamber 167 is only configured as an example to receive a smear sample, i.e., to receive a sampling device with attached (angebundene) sample material and is fluidically connected to the two valves 134, 135 in the second functional module. In a similar manner, the additional second functional module 262 includes a sample input chamber 168 with an exhaust device 192, which is fluidically connected to the two valves 137, 138. Here, the sample input chamber 168 is only configured as an example in the present embodiment to input a liquid sample. The second functional module 261 and the additional second functional module 262 are fluidically connected to the second channel interface via valves 134, 137.The second functional module 261 and the additional second functional module 262 are connected to the third channel interface 265 fluidly via valves 135, 138, through which there is only an exemplary fluid connection with the pump module 230 and with the third functional module 270 for filtering the sample material. The second functional module 261 can be separated from the rest of the microfluidic network 105 by the closing of valves 134, 135, and the additional second functional module 262 can be separated from the rest of the microfluidic network 105 by the closing of valves 137, 138. In the present embodiment, the third functional module 270 includes a filter element 170 in addition to four microfluidic valves 139, 140, 141, 142, which is only an exemplary silicate filter and is only configured to filter species from the sample material. Here, the closing of valves 139, 140 connected to the third channel interface 265 and the fourth functional module 280 fluids causes the fluid flow via the filter element 170 to be diverted. By closing the valves 139, 141, the third functional module 270 can be separated from the functional modules 250, 261, 262 and the pump module 230, and by closing the valves 140, 142, the third functional module 270 can be separated from the fourth functional module 280. In the present embodiment, the fourth functional module 280 is configured to store the fluid used in the network 105. To this end, the fourth functional module 280 only has, by way of example, a liquid storage chamber 180 with an exhaust device 193 and two valves 143, 144. In another embodiment, the fourth functional module 280 can be additionally configured to output sample material. The fourth functional module 280 is fluidically connected to the third functional module 270 and the connecting channel 125 via the fourth channel interface 285 in the present embodiment. Here, the valve 144 is only exemplarily configured as a stop valve and is arranged on the connecting channel 125. Therefore, by closing the valve 144, the entire first sub-network 110 can be separated from the remaining microfluidic network 105. In the present embodiment, the connecting channel 125 is a fluid connection between the fourth functional module 280 of the first subnetwork 110 and the first functional module 290 of the second subnetwork 120 for amplifying sample material. The first functional module 290 of the second subnetwork 120 is configured in the present embodiment for amplifying sample material and for this purpose only exemplarily comprises three active microfluidic pump chambers 153, 154, 155 arranged in a row, which are only exemplarily enclosed by two microfluidic valves 145, 146. Here, the valve 145 is directly arranged on the connecting channel 125 in the present embodiment and is configured as a stop valve. Therefore, the entire second subnetwork 120 can be separated from the rest of the microfluidic network 105 by closing the valve 145.In the present embodiment, the second subnetwork 120 also has a second functional module 295, which has: four valves 147, 148, 149, 150; an active (aktive) microfluidic pump chamber 156; a passive (passive) microfluidic chamber 160 and an exhaust device 194. The first functional module 290 and the second functional module 295 are fluidly connected to each other by valves 146, 147. Therefore, the separation of the two functional modules 290, 295 from each other can be achieved not only by means of the valve 146 of the first functional module 290 but also by means of the valve 147 of the second functional module 295. The second functional module 295 of the second subnetwork 120 is only exemplarily configured to provide at least one amplification reaction bead. The amplification reaction bead is only exemplarily a freeze-dried or freeze-dried reagent for producing an amplification reaction mixture.

[0062] Figure 3 Shown is a schematic diagram of a microfluidic device 100. The device 100 shown here corresponds to or is similar to the device described in the previous figure. In the diagram shown here, functional modules 250, 261, 262, 270, 280, 290, 295 and pump module 230 are shown in a simplified manner without each microfluidic element. At this, functional modules 250, 261, 262, 270, 280, 290, 295 and pump module 230 are arranged with a linear topological structure. In addition, functional modules 250, 261, 262, 270, 280 and pump module 230 are configured as the components of the first subnetwork 110 and functional modules 290, 295 are configured as the components of the second subnetwork 120, wherein the first subnetwork 110 and the second subnetwork 120 are connected to each other by just a connecting channel 125. The selected topology can, by way of example only, reduce the size of the dead volumes, reduce the number of pumping steps and prevent undesired microfluidic crosstalk between different process steps.

[0063] Figure 4100. The device 100 shown here corresponds to or is similar to the device with the described network depicted in the previous figure. In addition to the microfluidic elements forming the network 105 of the microfluidic device 100, the control channels for controlling the active microfluidic valves 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150 and the pump chambers 151, 152, 153, 154, 155, 156 are also shown as dashed lines. In this particularly advantageous embodiment, these twenty-six active microfluidic elements 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156 are actuated by means of a compact actuation interface 400. The actuation interface 400 comprises, merely by way of example, twenty actuation interfaces 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, which can also be referred to as actuation ports. In the present embodiment, the control port is a pneumatic interface, through which the active microfluidic elements 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156 are actuated only by applying an overpressure or underpressure. Thus, a total of six-way multiplexing is achieved, which is derived from the difference between the number of twenty-six elements and twenty ports. In the figure shown here, six branches belonging to the pneumatic control channel that can achieve multiple detection are shown in the form of black nodes. The branching of the control channel is either realized directly at the control port or at a suitable point of the control channel. In the embodiment shown, the branching is only realized directly at the control interface 409 by way of example. The control interface 409 is designed merely as an example for jointly controlling the valve 141 of the third functional module 270 of the first subnetwork 110 via the first control channel 431 and the valve 148 of the second functional module 295 of the second subnetwork 120 via the second control channel 432. In the present exemplary embodiment, the first shutoff valve 144 and the second shutoff valve 145 can be controlled in a similar manner via the valve control interface 418 for applying pressure.Thus, the connecting channel 125 can be opened or closed and the individual subnetworks 110, 120 can be separated from each other using the valve control interface 418. In contrast, the second control interface 410 in this embodiment has a first branch 441 and a second branch 442 and is therefore configured to jointly control the valve 131 of the first functional module 250 of the first subnetwork 110 and the valves 149, 150 of the second functional module 295 of the second subnetwork 120. In addition, the control interface 400 includes a further control interface 401 for applying pressure, wherein the further control interface 401 in this embodiment is connected to the valve 132 of the first functional module 250 of the first subnetwork 110 via a further control channel 451. The second further control interface 402 is connected, only as an example, to the pump chamber 152 of the pump module 230 of the first subnetwork 110, the third further control interface 403 is connected to the valve 137 of the additional second functional module 262 of the first subnetwork 110, the fourth further control interface 404 is connected to the valve 138 of the additional second functional module 262 of the first subnetwork 110, the fifth further control interface 405 is connected to the valves 139, 140 of the third functional module 270 of the first subnetwork 110, the sixth further control interface 406 is connected to the valve 139, 140 of the fourth functional module 280 of the first subnetwork 110. 143, an eighth further control interface 408 is connected to the valve 142 of the third functional module 270 of the first subnetwork 110, an eleventh further control interface 411 is connected to the valve 133 of the first functional module 250 of the first subnetwork 110, a twelfth further control interface 412 is connected to the valves 134, 135 of the second functional module 261 of the first subnetwork 110, a thirteenth further control interface 413 is connected to the pump chamber 151 of the pump module 230 of the first subnetwork 110, and a fourteenth control interface 414 is connected to the valve 136 of the pump module 230 of the first subnetwork 110. Similarly, in this embodiment, the elements of the second subnetwork 120 of the device 100 can also be controlled by means of the control interface 400. Thus, merely by way of example, the seventh further control interface 407 is connected to the pump chamber 153 of the first functional module 290 of the second sub-network 120, the fifteenth further control interface 415 is connected to the valve 146 of the first functional module 290 of the second sub-network 120, the sixteenth further control interface 416 is connected to the pump chamber 155 of the first functional module 290 of the second sub-network 120, the seventeenth further control interface 417 is connected to the pump chamber 154 of the first functional module 290 of the second sub-network 120, the nineteenth further control interface 419 is connected to the valve 147 of the second functional module 295 of the second sub-network 120, and the twentieth further control interface 420 is connected to the pump chamber 156 of the second functional module 295 of the second sub-network 120.

[0064] Figure 5 Shown is a schematic diagram of an embodiment of a microfluidic device 100. The device 100 shown here corresponds to or is similar to the device depicted in the previous figures.

[0065] Optionally, with Figure 3 In contrast to the described device, an additional fourth functional module 580 for storing a liquid is shown instead of an additional second functional module for supplying a sample substance.

[0066] According to Figure 3 Unlike the described device, according to the present embodiment, a first microfluidic pump chamber 151 and a second microfluidic pump chamber 152 are used to transport liquid between the functional modules 250 , 261 , 270 , 280 , 290 , 295 , 580 .

[0067] In the illustration shown here, functional modules 250, 261, 270, 280, 290, 295, 580 are shown in a simplified manner without individual microfluidic elements. Here, functional modules 250, 261, 270, 280, 290, 295, 580 are arranged in a linear topology. Functional modules 250, 261, 270, 280, 580 and pump chambers 151, 152 are configured as components of the first subnetwork 110 and functional modules 290, 295 are configured as components of the second subnetwork 120, wherein the first subnetwork 110 and the second subnetwork 120 are connected to each other via exactly one connecting channel 125.

[0068] The first microfluidic pump chamber 151 is connected between the first functional module 250 for providing liquid reagents and the third functional module 270 for filtering the sample material. For example, the first interface of the first microfluidic pump chamber 151 is coupled to the interface of the first functional module 250, to the first interface of the second functional module 261, and to the first interface of the additional fourth functional module 580. The second interface of the first microfluidic pump chamber 151 is exemplarily coupled to the first interface of the third functional module 270 and to the second interface of the additional fourth functional module 580. Therefore, the first microfluidic pump chamber 151 is connected in parallel with the optional additional fourth functional module 580.

[0069] The second microfluidic pump chamber 152 is connected between the second functional module 261 and the interface of the first subnetwork 110 coupled to the connecting channel 125. For example, the first interface of the second microfluidic pump chamber 152 is coupled to the second interface of the second functional module 261. The second interface of the second microfluidic pump chamber 152 is exemplarily connected to the interface of the fourth functional module 280 for storing liquid.

[0070] In this way, a series connection between the microfluidic pump chambers 151, 152 and the third functional module 270 can be achieved, which allows the microfluidic pump chambers 151, 152 to be operated in such a way that they jointly cause a pressure difference between the interfaces of the third functional module 270. The first microfluidic pump chamber 151 can be operated, for example, in such a way that the first microfluidic pump chamber 151 causes an overpressure at the first interface of the third functional module 270. At the same time, the second microfluidic pump chamber 152 can be operated in such a way that the second microfluidic pump chamber 152 causes an underpressure at the second interface of the third functional module 270.

[0071] Figure 6 1 shows a schematic diagram of an embodiment of a microfluidic device 100. The device 100 shown here corresponds to or is similar to the device depicted in the previous figure and comprises a microfluidic network 105, which is divided into a first subnetwork 110 and a second subnetwork 120. In the present embodiment, the microfluidic elements of the network 105 are arranged in a plurality of separable functional modules within the subnetworks 110, 120, wherein the individual functional modules are each indicated in the illustration shown here by a surrounding rectangular frame formed by a dash-dotted line.

[0072] The microfluidic device 100 substantially corresponds to Figure 2 The depicted device, wherein the essential difference lies in the arrangement of the microfluidic pump chambers 151 , 152 .

[0073] Optionally, with Figure 2 The device described differs in that instead of the additional second functional module for supplying sample material, an additional fourth functional module 580 for storing liquid is shown. The additional fourth functional module 580 comprises an additional liquid storage chamber 680, a venting device 192 and, by way of example, three valves 137, 138, 638.

[0074] In detail, in this embodiment, the subnetwork 110 for purifying sample materials includes a pump module, which is used to transport fluid and sample materials dissolved therein within the network 105 or between different functional modules. To this end, the pump module only exemplarily includes two active microfluidic pump chambers 151, 152 and microfluidic valves 136, 651.

[0075] In addition, the first subnetwork 110 has a first functional module 250 for providing a liquid reagent. In this first functional module, only three pre-storage chambers 161, 162, 163 are arranged exemplarily, for pre-storing liquid reagents stably for a long time. Liquid reagents are only exemplarily aqueous solutions, such as buffer solutions for treating sample substances or their components. In another embodiment, mineral oil, silicone oil or fluorinated hydrocarbons can also be stored in the pre-storage chamber. In the present embodiment, each pre-storage chamber 161, 162, 163 is connected to microfluid valves 131, 132, 133 fluids respectively, and the microfluid valves are connected to each other fluidically via the first channel interface 255 and are connected to the second channel interface 257 fluids. The first functional module 250 can be separated from the remaining microfluidic network 105 by closing valves 131, 132, 133.

[0076] In the present embodiment, the first functional module 250 is connected to the microfluidic valve 651 (which is connected in series with the microfluidic pump chamber 151), to the second functional module 261 for inputting the sample substance, and to the additional fourth functional module 580 for inputting the sample substance only by way of example via the second channel interface 257. The first interface of the first pump chamber 151 is connected to the second channel interface 257 via the valve 651.

[0077] The second functional module 261 comprises a sample input chamber 167 with a venting device 191. The sample input chamber 167 is designed merely as an example for receiving a smear sample, ie, for receiving a sampling device with attached sample material, and is fluidically connected within the second functional module 261 to the two valves 134, 135.

[0078] The second functional module 261 and the additional fourth functional module 580 are fluidically connected to the second channel interface 257 via valves 134, 137. The additional fourth functional module 580 is in turn fluidically connected to the third channel interface 165 via valves 138, 638, through which there is only an exemplary fluid connection with the first pump chamber 151 and the third functional module 270 for filtering the sample material. The second functional module 261 can be separated from the rest of the microfluidic network 105 by closing the valves 134, 135, and the additional fourth functional module 262 can be separated from the rest of the microfluidic network 105 by closing the valves 137, 138, 638.

[0079] In the present embodiment, the third functional module 270 includes a filter element 170 in addition to four microfluidic valves 139, 140, 141, 142, which is only exemplarily a silicate filter and is only exemplarily configured to filter species from the sample material. Here, the closing of the valves 139, 140 connected in series between the third channel interface 265 and the fourth channel interface 285 causes the fluid flow through the filter element 170 to be redirected. The closing of the valves 139, 141 can separate the third functional module 270 from the functional modules 250, 261, 262 and the pump module 230, and the closing of the valves 140, 142 can separate the third functional module 270 from the fourth functional module 280.

[0080] In the present embodiment, the fourth functional module 280 is configured to store the fluid used in the network 105. For this purpose, the fourth functional module 280 only has, by way of example, a liquid storage chamber 180 with an exhaust device 193 and two valves 143, 144. In another embodiment, the fourth functional module 280 can be additionally configured to output the sample material. The fourth functional module 280 is fluidically connected to the fourth channel interface 285 via the second pump chamber 252 and the valve 136 in the present embodiment.

[0081] Therefore, the third functional module 270 for filtering the sample material is connected between the third channel interface 265 and the fourth channel interface 285. The second interface of the first pump chamber 151 is directly connected to the third channel interface 265, and the second interface of the second pump chamber 152 is connected to the third channel interface 265 via the valve 136.

[0082] The fourth channel interface 285 is connected to the connecting channel 125 via a valve 144, which is only exemplarily configured as a shut-off valve. Thus, the entire first subnetwork 110 can be separated from the rest of the microfluidic network 105 and in particular from the second subnetwork 120 by closing the valve 144. In the present embodiment, the connecting channel 125 is a fluid connection between the fourth functional module 280 of the first subnetwork 110 and the first functional module 290 of the second subnetwork 120 for amplifying sample material.

[0083] The first functional module 290 of the second subnetwork 120 is designed in this embodiment for amplifying the sample material and for this purpose only comprises three active microfluidic pump chambers 153, 154, 155 arranged in a row, which are only exemplarily comprised by two microfluidic valves 145, 146. Here, the valve 145 is arranged directly on the connecting channel 125 in this embodiment and is configured as a shut-off valve. Therefore, the entire second subnetwork 120 can be separated from the rest of the microfluidic network 105 by closing the valve 145. In this embodiment, the second subnetwork 120 also has a second functional module 295, which has four valves 147, 148, 149, 150; an active microfluidic pump chamber 156; a passive microfluidic chamber 160 and an exhaust device 194. The first functional module 290 and the second functional module 295 are fluidically connected to each other via valves 146, 147. Therefore, the mutual separation of the two functional modules 290, 295 can be achieved not only by means of the valve 146 of the first functional module 290, but also by means of the valve 147 of the second functional module 295. The second functional module 295 of the second subnetwork 120 is only configured to provide at least one amplification reaction bead by way of example. The amplification reaction bead is only exemplarily a lyophilized or freeze-dried reagent for producing an amplification reaction mixture.

[0084] Figure 7Schematic diagram of an embodiment of a microfluidic device 100 is shown. The device 100 shown here corresponds to or is similar to the device with the described network depicted in the previous figure. In addition to the microfluidic elements forming the network 105 of the microfluidic device 100, control channels for controlling active microfluidic valves 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 638, 651 and pump chambers 151, 152, 153, 154, 155, 156 are also shown as dashed lines. In the present embodiment, the active microfluidic elements 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 638, 651 are controlled by means of a compact control interface 400. The control interface 400 merely includes twenty control interfaces 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, which can also be referred to as control ports. In the present embodiment, the control port is a pneumatic interface, through which the active microfluidic elements 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 638, 651 are actuated only by applying an overpressure or underpressure. This enables multi-channel multiple detection. Figure 7 In FIG. 1 , the associated branches of the pneumatic control channel that enable multiple detection are shown in the form of black nodes. The branching of the control channel is realized either directly at the control port or at a suitable point of the control channel.

[0085] therefore, Figure 7 A schematic diagram of a network 105 of another advantageous embodiment of a microfluidic analysis device 100 is shown having a linear topology.

[0086] Compared to the previous embodiment, the network 105 of another embodiment of the microfluidic analysis device 100 is composed of microfluidic channels shown schematically as solid lines, which connect different microfluidic elements to each other. In this other embodiment, the network 105 of the microfluidic analysis device 100 is particularly outstanding in that:

[0087] - twenty-two active microfluidic valves 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 638, 651,

[0088] - six active microfluidic pump chambers 151, 152, 153, 154, 155, 156,

[0089] - a passive microfluidic chamber 160,

[0090] - three pre-storage chambers 161, 162, 163 with exhaust openings, which are used to pre-store liquid reagents stably for a long time,

[0091] - a chamber 167 enabling sample input,

[0092] - a filter element 170 which enables extraction of components from the liquid,

[0093] - two liquid storage chambers 180, 680 for receiving liquid after processing in the microfluidic network 105, and

[0094] - Three exhaust devices 191 , 192 , 193 for exhausting the microfluidic network 105 .

[0095] In this embodiment, a total of twenty-eight active microfluidic elements 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 638, 651 can be controlled by a pneumatic control channel, which is Figure 6 In the figure, the lines perpendicular to the microfluidic channel branches are shown. Figure 7 A detailed schematic diagram of such an advantageous exemplary embodiment of the microfluidic analysis device 100 including the configuration of the pneumatic actuation channels is given in .

[0096] As in the previous variant embodiment, the arrangement and connection of the mentioned elements for the microfluidic network 105 are selected as a particularly advantageous linear topology. As shown in the accompanying drawings, the microfluidic network 105 of the microfluidic analysis device 100 consists of a first subnetwork 110 and a second subnetwork 120, wherein the first subnetwork is configured to purify the sample material and the second subnetwork 120 is configured to amplify the sample material. The two subnetworks 110, 120 are connected to each other via a microfluidic connection channel 210. Since the microfluidic treatment is carried out continuously, i.e. sequentially, within the framework of the execution of the test process within the two subnetworks 110, 120, it is possible to control the combination of active microfluidic elements belonging to different subnetworks 110, 120, if necessary, through a common control channel, without thereby having an adverse effect on the microfluidic treatment.

[0097] from Figure 7 As can be seen from the circuit diagram of this advantageous embodiment of the microfluidic device 100 shown in FIG. 1 , only twenty pneumatic control ports 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720 are used in a particularly advantageous manner to control a total of twenty pneumatic control ports. Eight active microfluidic elements 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 638, 651, wherein this can be achieved by a total of eight branches of the pneumatic control channel. The branching points of the pneumatic control channel are at Figure 7 , respectively, in a schematic manner by means of black circular nodes on the pneumatic control channels shown with dashed lines. Thus, this embodiment shows that the selected design according to the invention of the microfluidic device 100 and the multiple detection when the elements are controlled can provide significant functional advantages, because on the one hand only a small number of pneumatic control ports are required for actuating the microfluidic elements, and on the other hand, due to the linear topology of the microfluidic network 105, no compromises have to be made with important restrictions in the execution of the microfluidic process. Therefore, by means of a particularly advantageous design according to the invention, it is possible to combine improved functionality with reduced costs for controlling active microfluidic elements. In addition, the separate execution of purification and amplification in separate subnetworks 110, 120 can advantageously reduce dead volumes, reduce the number of rinsing steps and prevent undesired microfluidic crosstalk between different process steps.

[0098] In addition, through Figure 6 and Figure 7 The advantageous embodiment of the microfluidic device 100 shown in FIG. 1 also enables the selection of particularly variable pumping strategies during the extraction of components of the sample material through the filter element 170 during the purification of the sample material.

[0099] with Figures 1 to 4 Compared with the first embodiment shown in Figure 6 and Figure 7 In another embodiment shown in FIG. 1 , two pump chambers 151 and 152 are integrated into the microfluidic network 105 in such a way that they are connected in series with the filter element 170. This makes it possible, for example, to improve the pumping of the sample liquid through the filter element 170 by combining the compression of the pump chamber 151 with the suction with the pump chamber 152, so that a particularly high pressure difference is present in the microfluidic system when the sample liquid is pumped through the filter element 170. In this way, for example, particularly highly viscous or viscous sample substances or inhomogeneous sample liquids with highly viscous sample components can be reliably pumped through the filter element 170 in an advantageous manner in order, for example, to achieve extraction or accumulation of sample components on the filter element 170.

[0100] In addition, the microfluidic separation of the first pump chamber 151 from the pre-storage chambers 161, 162, 163 and the sample input chamber 167 is correspondingly achieved by at least two of the microfluidic valves 131, 132, 133, 134, 651, thereby essentially ensuring a particularly reliable microfluidic separation of these liquid paths when pressure is applied to the microfluidic pump chamber 151.

[0101] In addition, Figure 7 In the detailed illustration in FIG. 1 , the functional modules 250 , 261 , 270 , 280 , 290 , 295 , 580 forming the sub-networks 110 , 120 of the microfluidic analysis device 100 are shown by surrounding rectangular boxes:

[0102] In detail, the subnetwork 110 for purifying sample materials consists of the following parts:

[0103] - a first functional module 250 for providing a liquid reagent,

[0104] a second functional module 261 for inputting a sample substance into the microfluidic device 100,

[0105] a third functional module 270 for filtering out species from the sample material,

[0106] - two fourth functional modules 280, 580 for storing liquid, and

[0107] - Two pump modules 730, 731 for establishing liquid transport between the different functional modules.

[0108] The subnetwork 120 for amplifying sample material consists of the following components:

[0109] - a first functional module 290 for amplification, and

[0110] - A second functional module 295 for providing beads for amplification reactions.

[0111] Figures 5 to 7 In another embodiment, an arrangement of functional modules 250 , 261 , 270 , 280 , 580 in first subnetwork 110 for purifying sample material and functional modules 290 , 295 in second subnetwork 120 for amplifying sample material is shown in different details in a linear topology.

[0112] As described above, in this advantageous embodiment, improved pumping of the sample liquid through the filter element 170 can be achieved by using two pumping modules 151, 152 connected on both sides to a third functional module 270 for filtering species from the sample material in the first subnetwork 110 for purifying the sample material.

[0113] For example, the actuation interface 718 is used to apply a first pressure to the first microfluidic chamber 151, and the actuation interface 709 is used to apply a second pressure to the second microfluidic chamber 152. Thus, the two pump chambers 151, 152 can be actuated independently of each other.

[0114] By way of example, the common control interface 703 is used to control the valves 138, 141 of the first subnetwork 110 via the first control channel 431 and to control the valve 148 of the second subnetwork 120 via the second control channel 432. Accordingly, the common control interface 701 is used not only for controlling the first functional module 250 of the first subnetwork 110 but also for controlling the second functional module 295 of the second subnetwork 120.

[0115] The valve actuation interface 713 is used to actuate the shutoff valves 144 , 145 .

[0116] Figure 8A schematic diagram of an embodiment of a microfluidic device 100 is shown. The device 100 shown here corresponds to or is similar to the device described in the previous figure. For illustration, a microfluidic network 105 is shown in a simplified manner in the figure shown here. In this embodiment, the microfluidic device 100 includes: two subnetworks 110, 120, which are connected to each other via a microfluidic connecting channel 125; and a pneumatic control interface 400, which has four control interfaces 409, 410, 418, 500 or 701, 703, 713, 500. The control interfaces 409, 410, 418, 500, 701, 703, 713, 500 are respectively constructed in this embodiment to control not only the microfluidic elements of the first subnetwork 110 but also the microfluidic elements of the second subnetwork 120. By means of this four-way multiplex detection, a total of eight active microfluidic elements of the device 100 can be controlled in an advantageous manner by means of four control ports, wherein four active microfluidic elements of each subnetwork 110, 120 are respectively controlled. In this case, multiplex detection is achieved by branching the control channels at a total of four nodes 409, 418, 441, 505 or 703, 713, 441, 505.

[0117] Fig. 9 1 shows a three-dimensional top view of an embodiment of a microfluidic device 100. The device 100 shown here corresponds to or is similar to the device described in the previous figure. In this embodiment, the device 100 has a reagent stick 600 arranged inside three pre-storage chambers 161, 162, 163 and having three grids, in which different liquid reagents can be pre-stored stably for a long time. Accordingly, the pre-storage chambers 161, 162, 163 can also be called reagent pre-storage chambers. In addition, in the previous Figures 2 to 4 Arranged merely as an example within the sample input chamber 167 of the second functional module depicted in FIG. 1 is a sampling device 605 which allows a smear sample located thereon to be transferred into the network 105 of the microfluidic device 100 .

[0118] Fig.10A top view of an embodiment of a microfluidic device 100 is shown. The device 100 shown here corresponds to or is similar to the device depicted in the previous figure. In the diagram shown here, some of the elements of the microfluidic device 100 depicted in the previous figure are shown by way of example. In detail, the microfluidic valve 146, the microfluidic pump chambers 151, 152, 153, 154, 155, 156, the microfluidic chamber 160, the three pre-storage chambers 161, 162, 163, the two sample input chambers 167, 168, the microfluidic filter element 170 and the liquid storage chamber 180 are indicated. In addition, a first subnetwork 110 for purifying sample material, a second subnetwork 120 for amplifying sample material and a pneumatic control interface 400 with another control interface 401 indicated by way of example are shown by way of dotted lines. The device has only 118×78 mm 2 In another embodiment, the overall size can be 50×25 mm. 2 Up to 300×200mm 2 , preferably 75×25mm 2 Up to 200×100mm 2 Furthermore, in this exemplary embodiment, the fluidic and pneumatic microchannels have a diameter of only 600×400 μm. 2 In another embodiment, the cross-sectional dimensions of the fluidic and pneumatic microchannels can be 100×100 μm. 2 Up to 3×3mm 2 , preferably 300×300μm 2 Up to 1×1mm 2 . The effective displacement of the microfluidic pump chamber is 20 μl in the present embodiment, the effective displacement of the microfluidic valve is only 125 nl by way of example, and the volume of the microfluidic chamber with the filter element is only 8 μl by way of example in the present embodiment. In other embodiments, the effective displacement of the microfluidic pump chamber can be 1 μl to 50 μl, preferably 5 μl to 30 μl, the effective displacement of the microfluidic valve can be 50 nl to 1 μl, preferably 100 nl to 300 nl, and the volume of the microfluidic chamber with the filter element can be 3 μl to 20 μl, preferably 5 μl to 10 μl. Here, for microfluidic processing inside the device 100, a pressure difference of only 700 mbar (overpressure or underpressure relative to atmospheric pressure) can be used in the present embodiment, which is used to generate a microfluidic flow by squeezing or suctioning by means of a pump chamber or by controlling the microfluidic flow by means of a valve. In another exemplary embodiment, the pressure difference can be 100 mbar to 2000 mbar, preferably 400 mbar to 1500 mbar.

[0119] Fig.11A partial three-dimensional top view of a microfluidic device 100 according to an embodiment is shown. The device 100 shown here corresponds to or is similar to the device depicted in the previous figure. In the accompanying drawings shown here, the microfluidic valve 131, the microfluidic pump chambers 151, 152, the sample input chamber 168, the microfluidic chamber with the filter element 170, the exhaust device 193 and the pneumatic control ports 405, 409, 410 are exemplarily indicated. The microfluidic device 100 in this embodiment is realized by two rigid polymer components 800, 805, which are connected to each other by a flexible diaphragm 810. The lower polymer component 800 is closed by another polymer film to seal the microchannels present in the polymer component. Therefore, the multilayer structure can realize fluid and pneumatic microchannels in particular on at least two different transverse planes. In this way, the fluid and pneumatic microchannels can intersect and can utilize the microchannels in the multilayer structure. Figure 4 The central and particularly compact design of the pneumatic control interface depicted in the figure realizes a particularly high degree of integration of the microfluidic device 100. By applying an overpressure or underpressure to the pneumatic control interface, a flexible polymer film can be offset in a recess existing on the microfluidic valve and pump chamber through a pneumatic microchannel, so as to realize the opening or closing of the microfluidic valve or pump chamber in this way. By means of pumping or discharging liquid by means of the pump chamber, the microfluid flow inside the network 105 can be accurately controlled in a suitable valve position. In other embodiments, for example, the following materials can be used to realize the microfluidic analysis device: mainly polymers, such as polycarbonate (PC), polystyrene (PS), styrene-acrylonitrile copolymer (SAN), polypropylene (PP), polyethylene (PE), cycloolefin copolymer (COP, COC), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS) or thermoplastic elastomer (TPE), such as polyurethane (TPU) or styrene block copolymer (TPS). Here, the device can be manufactured, for example, by a batch manufacturing method, such as injection molding, injection extrusion, thermoforming, stamping or laser transmission welding.

[0120] Fig.12 A partial three-dimensional bottom view of a microfluidic device 100 according to an embodiment is shown. The device 100 shown here corresponds to or is similar to the device described in the previous figure. In the figure shown here, the microfluidic valve 131, the microfluidic pump chambers 151, 152, the sample input chambers 167, 168, the microfluidic chamber with the filter element 170, the exhaust device 193 and the pneumatic control port 405 are marked as examples.

[0121] Fig.13A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown. The device operated by the method can be the device described in the previous figure. Method 1000 includes a step 1005 of extracting sample material when using the first subnetwork. Here, the sample material in the subnetwork is only purified and sample material, such as DNA or RNA, is extracted from the sample material and transported to the microfluidic network. Then, optionally, a step 1010 of transporting the sample material from the first subnetwork to the second subnetwork is performed, wherein a solution with the previously extracted sample material is transported from the first subnetwork to the second subnetwork. In the optional next step 1015 of amplifying the sample material when using the second subnetwork, the sample material is amplified in the second subnetwork and thus made available for, for example, fluorescence determination. In another embodiment of method 1000, the step 1005 of extraction or the steps 1010, 1015 of transport and amplification can be cancelled. For example, as long as the species to be detected is already present in the sample liquid input in an extracted form, the first step 1005 of extraction can be omitted. If only purification or extraction of the sample material is carried out in the device and the sample material is removed from the microfluidic device again, for example after carrying out the first step 1005 of extraction, then for example the second step 1010 of transport and the third step 1015 of amplification can be omitted.

[0122] Fig.14 A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown. The method 1000 shown here corresponds to or is similar to the method described in the previous Fig.13 The method described in , the difference is that each step 1005, 1010, 1015 has an additional sub-step. In the present embodiment, the step 1005 of extraction includes the sub-step 1105 of mixing and the sub-step 1110 of separation and the sub-step 1115 of lysis and the sub-step 1120 of filtration and the sub-step 1125 of washing. In the present embodiment, the step 1010 of transportation includes the sub-step 1130 of elution, and the step 1015 of amplification includes the sub-step 1135 of dissolution and the sub-step 1140 of replication and the sub-step 1145 of detection. In the sub-step 1105 of mixing, only the liquid sample input into the sample input chamber is mixed with the binding buffer by way of example. The mixing is carried out in particular when using the first functional module, the additional second functional module, the pump module and the plurality of elements mentioned below, the elements being: microfluid valve, microfluid pump chamber, sample input chamber and exhaust device. In the present embodiment, the binding buffer is pre-stored in exactly one pre-storage chamber in the three pre-storage chambers of the first sub-network. In the present embodiment, the adjacent functional modules comprise microfluidic valves, which are closed in this sub-step 1105 , thereby preventing undesired microfluidic crosstalk with the adjacent functional modules.

[0123] In the present embodiment, in the sub-step 1110 of disengagement, the disengagement of the sample material is carried out in the sample input chamber, and the sample material initially exists in a state of being attached to the sampling device input into the sample input chamber. The disengagement is only performed by means of transporting liquid, which is introduced into the chamber in particular when using the first functional module and the second functional module and the pump module and a plurality of elements mentioned below, wherein the elements are: microfluid valve, microfluid pump chamber, pre-storage chamber, sample input chamber and exhaust device. The transport liquid is only pre-stored in exactly one pre-storage chamber in the pre-storage chamber in an exemplary manner. The adjacent functional module particularly comprises a microfluid valve, which is closed in this sub-step 1110, thereby preventing the undesirable microfluid crosstalk with the adjacent functional module.

[0124] In the present embodiment, in the sub-step 1115 of lysis, lysis buffer is added to the sample material in at least one sample input chamber input into the sample input chamber, and the sample material or its components are temperature-adjusted to cause the heat-induced lysis of the components of the sample material. The sample material components to be lysed in this sub-step 1115 are only bacteria by way of example. In another embodiment, for example, other cells can be used. The lysis is carried out in particular using the first functional module, the second functional module and the additional second functional module and the pump module and a plurality of the elements mentioned below, the elements being: a microfluid valve, a microfluid pump chamber, a pre-storage chamber, a sample input chamber and an exhaust device. The lysis buffer is only pre-stored in exactly one pre-storage chamber in the pre-storage chamber by way of example. The adjacent functional module particularly comprises a microfluid valve, which is closed in this sub-step 1115, thereby preventing the undesired microfluid crosstalk with the adjacent functional module. In an alternative embodiment of the lysis substep 1115 , after the components of the sample substance have accumulated on the filter element in the filtration substep 1120 , the components of the sample substance can be lysed thermally by controlling the temperature of the filter element.

[0125] In the present embodiment, in the sub-step 1120 of filtering, the components of the sample material in at least one sample input chamber input into the sample input chamber are filtered and attached when using a filter element, so that the components of the sample material accumulate on the filter element. The filtering is performed in particular when using the third functional module, the fourth functional module, the second functional module or the additional second functional module and the pump module and a plurality of the following elements, the elements being: a microfluid valve, a microfluid pump chamber, a sample input chamber, a filter element, a liquid storage chamber, and an exhaust device. The adjacent functional module particularly comprises a microfluid valve, which is closed in this sub-step 1120, thereby preventing undesirable microfluid crosstalk with the adjacent functional module in this sub-step. Here, for example, a binding buffer with the sample material is pumped from one of the sample input chambers via the filter element into the liquid storage chamber by means of a pumping module, wherein the components of the sample material, such as DNA or RNA, are attached to the filter element and concentrated. In the present embodiment, the sub-step 1120 of filtering is performed after performing the sub-step 1105 of mixing, the sub-step 1110 of separation, and the sub-step 1115 of lysis. In another embodiment, the sub-step of filtering 1120 can be carried out before or after the sub-step of lysing, depending on the precise embodiment of the method: if the lysis is carried out in one of the sample input chambers, the sub-step of filtering can be carried out after the sub-step of lysing, whereas if the lysis is carried out on the filter element, the sub-step of filtering can be carried out before the sub-step of lysing 1115.

[0126] In the present embodiment, in the sub-step 1125 of rinsing, the microfluidic network is rinsed with a wash buffer, for example, to eliminate binding buffer residues present in the microfluidic network after the sub-step 1120 of filtering. The rinsing is performed in particular using the first functional module, the third functional module and the fourth functional module and the pump module and a plurality of the following elements, the elements being: a microfluidic valve, a microfluidic pump chamber, a pre-storage chamber, a liquid storage chamber and an exhaust device. The wash buffer is pre-stored only exemplarily in exactly one of the pre-storage chambers.

[0127] In the present embodiment, in the sub-step 1130 of elution, the sample material existing on the filter element is disengaged downwards, so that it can be provided for the molecular diagnosis detection carried out by means of amplification reaction. The sample material is only exemplarily DNA, and in another example, the sample material can also be RNA. For this reason, only exemplarily the elution buffer is pumped to the filter element, so that the sample material existing on the filter element is transferred to the elution buffer. In the correlation with elution, in the present embodiment, the elution buffer with sample material will also be transported to the second subnetwork via the microfluidic connecting channel from the first subnetwork. Described elution is especially carried out when using the first functional module, the third functional module and the fourth functional module of the first subnetwork and the first functional module and pump module of the second subnetwork and a plurality of elements mentioned below: microfluid valve, microfluid pump chamber, microfluid connecting channel, pre-storage chamber, liquid storage chamber and exhaust device. Described elution buffer is only exemplarily pre-stored in just a pre-storage chamber in the pre-storage chamber.

[0128] In the present embodiment, in the sub-step 1135 of dissolving, use the elution buffer containing sample material, so that freeze-dried or lyophilized reagent (it can also be called reaction beads) dissolves and provides the reaction mixture for subsequent amplification reaction in this way. This is only exemplarily a kind of master mixture for carrying out polymerase chain reaction. The dissolving is especially carried out when using the first functional module and the second functional module of the second subnetwork and a plurality of elements mentioned below, and the element is: microfluid valve, microfluid pump chamber, microfluid chamber and exhaust device. In the present embodiment, freeze-dried or lyophilized reagent or reaction beads are present in pump chamber or passive microfluid chamber. In the present embodiment, when using the pump chamber, the elution buffer with sample material is pumped to at least one element in the element for dissolving reaction beads. After the reaction beads dissolve, only exemplarily the reaction mixture produced thereby is transported to the first functional module of the second subnetwork from the second functional module of the second subnetwork.

[0129] In the present embodiment, at least one amplification reaction is carried out in the sub-step 1140 of duplication in order to amplify the sample material present in the reaction mixture. The duplication is carried out in particular using the first functional module of the second sub-network and a plurality of the elements mentioned below, the elements being: microfluidic valves, microfluidic pump chambers. The duplication is only exemplarily achieved by polymerase chain reaction. In another embodiment, the duplication can also be achieved by an isothermal amplification method. Therefore, within the scope of the sub-step of duplication, the microfluidic pump chamber in which the reaction mixture is present can also be temperature-controlled in order to provide suitable physical conditions that enable the amplification reaction to be performed.

[0130] In the present embodiment, a signal is detected in the sub-step 1145 of detection in order to detect the progress of at least one amplification reaction within the scope of the sub-step 1140 of replication. The signal is merely exemplarily an optical signal, such as a fluorescent signal, which is based on at least one fluorescent dye, which indicates the progress of at least one amplification reaction. In another embodiment, the sub-step 1145 of detection can be performed simultaneously with the sub-step 1140 of replication or after the sub-step 1140 of replication. Optionally, the signal or the parameter derived therefrom is also output in the sub-step 1145 of detection in order to output the result of the sample analysis performed in the microfluidic analysis device to the user.

[0131] In other embodiments of the method, individual sub-steps can be omitted or performed repeatedly or exchanged with other sub-steps in terms of sequence, which is described by way of example in the following embodiments.

[0132] Fig.15 A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown. The method 1000 shown here corresponds to or is similar to the method described in the previous Fig.13 and Fig.14 In this variant of method 1000, substeps 1105 of mixing, 1115 of lysing, 1120 of filtering, 1125 of washing, 1130 of eluting, 1135 of dissolving, 1140 of replicating, and 1145 of detecting are performed in succession.

[0133] Fig.16 A flow chart of a method 1000 for operating a microfluidic device according to an embodiment is shown. The method 1000 shown here corresponds to or is similar to the method described in the previous Fig.13 , 14 and 15. In this variant of method 1000, the substeps 1110 of detaching, 1120 of filtering, 1115 of lysing, 1125 of washing, 1130 of eluting, 1135 of dissolving, 1140 of replicating, and 1145 of detecting are performed in succession.

[0134] Fig.17 14 shows a schematic diagram of an exemplary embodiment of an analysis device 1400 for receiving a microfluidic device. The analysis device 1400 is designed merely as an example for receiving a microfluidic device by means of an input opening 1405 as described above. Figures 1 to 12 The microfluidic device described in the embodiment of the present invention is used to perform an analysis process in the device. Here, the analysis device 1400 in the present embodiment includes a control device 1410, which is configured to control the microfluidic device described in the embodiment of the present invention. Figures 13 to 16The steps of the method described in relation to the device are controlled.

Claims

1. A microfluidic device (100) for analyzing a sample material, wherein: The device (100) comprises a microfluidic network (105) having a first subnetwork (110) for purifying a sample material, The first sub-network (110) includes: a first functional module (250) for providing a liquid reagent; a second functional module (261) for inputting a sample material; a third functional module (270) for filtering the sample material; a fourth functional module (280) for storing liquid; and a first microfluidic pump chamber (151) and a second microfluidic pump chamber (152) for establishing fluid transport. It is characterized in that The first microfluidic pump chamber (151) and the second microfluidic pump chamber (152) are connected in series with a third functional module (270) for filtering sample material.

2. The microfluidic device (100) according to claim 1 has a second subnetwork (120) for amplifying sample material, wherein the second subnetwork is connected to the first subnetwork (110) via a connecting channel (125), wherein: The first subnetwork (110) and the second subnetwork (120) are separable from each other, wherein the second subnetwork (120) includes at least one first functional module (290) for amplifying sample material and a second functional module (295) for dissolving at least one amplification reaction bead.

3. The microfluidic device (100) according to any one of the preceding claims, wherein the first sub-network (110) and the second sub-network (120) are arranged in a linear topology.

4. A microfluidic device (100) according to any of the preceding claims, wherein the device (100) has a control interface (718) for applying a first pressure to a first microfluidic pump chamber (151) and a control interface (709) for applying a second pressure to a second microfluidic pump chamber (152), so as to cause a pressure difference on a third functional module (270) for filtering sample material by squeezing the first microfluidic pump chamber (151) and suctioning the second microfluidic pump chamber (152).

5. A microfluidic device (100) according to any of the preceding claims, wherein the first interface of the first microfluidic pump chamber (151) is connected to a first functional module (250) for providing a liquid reagent and to a second functional module (261) for inputting a sample substance, the second interface of the first microfluidic pump chamber (151) is connected to a first interface of a third functional module (270) for filtering the sample material, the first interface of the second microfluidic pump chamber (152) is connected to the second functional module (261) for inputting the sample substance, and the second interface of the second microfluidic pump chamber (152) is connected to a second interface of the third functional module (270) for filtering the sample substance.

6. A microfluidic device (100) according to claim 5, wherein the third functional module (270) includes a filter element (170) and at least one microfluidic valve (139, 140'), the filter element is detachably connected to the first interface of the third functional module (270) and is detachably connected to the second interface of the third functional module (270), and the microfluidic valve is connected between the first interface and the second interface of the third functional module (270).

7. The microfluidic device (100) according to any one of claims 5 to 6, wherein: The second functional module (261) includes a sample input chamber (167) for inputting sample material, wherein the sample input chamber (167) is detachably connected to a first interface of the second functional module (261) and is detachably connected to a second interface of the second functional module (261), wherein the first interface of the first microfluidic pump chamber (151) is connected to the first interface of the second functional module (261), and the first interface of the second microfluidic pump chamber (152) is connected to the second interface of the second functional module (261).

8. The microfluidic device (100) according to claim 2, wherein the device (100) has a common control interface (703) for applying pressure, wherein: The common control interface (703) is connected to elements of functional modules (250, 261, 270, 280, 580) of a first subnetwork (110) via a first control channel (431) and to elements of functional modules (290, 295) of a second subnetwork (120) via a second control channel (432).

9. A microfluidic device (100) according to claim 2, wherein the first subnetwork (110) has a first shut-off valve (144) for closing the connecting channel (125) and / or the second subnetwork (120) has a second shut-off valve (145) for closing the connecting channel (125).

10. The microfluidic device (100) according to claim 9, comprising a valve control interface (713) for applying pressure, wherein: The first stop valve (144) and the second stop valve (145) can be controlled by means of a valve control interface (713).

11. The microfluidic device (100) according to any one of the preceding claims, wherein the fourth functional module (280) of the first subnetwork (110) is configured to output a liquid containing a sample material.

12. The microfluidic device (100) according to any one of the preceding claims, wherein: The first subnetwork (110) has an additional fourth functional module (580) for storing a liquid, wherein the first microfluidic pump chamber (151) is connected in parallel to the additional fourth functional module (580).

13. A method (1000) for operating a microfluidic device (100) according to any one of the preceding claims, wherein the method (1000) comprises the following steps (1005, 1010, 1015): extracting (1005) a sample material using the first subnetwork (110); It is characterized in that The extraction step (1005) includes a filtering sub-step (1120), in which a pressure difference is generated on the third functional module (270) by combining the squeezing of the first microfluidic pump chamber (151) and the suction with the second microfluidic pump chamber (152) to cause filtering of the sample material.

14. The method (1000) according to claim 13 comprises the steps of transporting (1010) the sample material from the first subnetwork (110) to the second subnetwork (120) and amplifying (1015) the sample material while using the second subnetwork (120).

15. The method according to claim 14, wherein: The extraction step (1005) has a mixing sub-step (1105) and / or a detachment sub-step (1110) and / or a lysis sub-step (1115) and / or a washing sub-step (1125), and / or wherein the transport step (1010) has an elution sub-step (1130), and / or wherein the amplification step (1015) has a dissolution sub-step (1135) and / or a replication sub-step (1140) and / or a detection sub-step (1145).

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