Microfluidic processing device and method for operating a microfluidic processing device

Abstract

The present invention relates to a microfluidic processing device (100) for processing a sample liquid, wherein the microfluidic processing device (100) has at least one microfluidic channel system (105), the microfluidic channel system having at least one filter branch (125) and a pumping branch (155) connected in parallel to the filter branch (125). In addition, the processing device (100) has at least one filter chamber (130) arranged in the filter branch (125) for receiving a filter element (135), wherein the filter branch (125) is fluidically coupled or can be coupled to a channel inlet (110) via a first, in particular T-shaped, channel intersection element and is fluidically coupled or can be coupled to a channel outlet (150) via a second, in particular T-shaped, channel intersection element, and wherein the filter chamber (130) can be fluidically separated from the rest of the channel system (105) by at least two filter valves (140a, 140b). In addition, the processing device (100) has a pumping mechanism (157) arranged in a pumping branch (155) for establishing a fluid flow in the channel system (105), wherein the filtering branch (125) is part of the channel system (105), wherein the pumping mechanism (157) includes at least one pumping valve (165a) and at least one pumping chamber (160a), and wherein the pumping branch (155) is fluidically coupled or capable of being coupled to the channel inlet (110) via a different joint of the first channel intersection element than the filtering branch (125) and is fluidically coupled or capable of being coupled to the channel outlet (150) via a different joint of the second channel intersection element than the filtering branch (125).

Description

Technical Field

[0001] The present invention relates to a microfluidic processing device for processing a sample liquid and a method for operating a microfluidic processing device. A computer program is also a subject of the present invention. Background Art

[0002] Microfluidic analysis systems, so-called lab-on-a-chip (LoCs), allow for automated, reliable, rapid, compact, and cost-effective processing of patient samples for medical diagnostics. By combining numerous operations for the controlled manipulation of fluids, complex molecular diagnostic test processes can be implemented on a lab-on-a-chip cartridge. Extracting components such as nucleic acids from samples, particularly sample liquids, is a crucial operation. Summary of the Invention

[0003] Against this background, the solution presented here describes an improved microfluidic processing device for processing a sample liquid, an improved method for operating the microfluidic processing device, a control device using this method, and finally a corresponding computer program. Advantageous developments and improvements of the described device are possible through the measures listed in the dependent claims.

[0004] The solution and the use of the processing device described herein advantageously achieve particularly high yields, i.e., high extraction efficiencies, when purifying sample liquids. The processing device described herein allows for a particularly space-saving arrangement of the microfluidic channels and the necessary connections and interfaces to the microfluidic network, thereby achieving a particularly compact implementation of a lab-on-a-chip cartridge. This, for example, enables particularly cost-effective and resource-saving production, for example due to reduced material usage.

[0005] A microfluidic processing device for processing a sample liquid is described, wherein the microfluidic processing device comprises at least one microfluidic channel system, the microfluidic channel system comprising at least one filter branch and a pumping branch connected in parallel with the filter branch. Furthermore, the processing device comprises at least one filter chamber disposed in the filter branch for accommodating a filter element, wherein the filter branch is fluidically coupled or capable of coupling to a channel inlet via a first channel intersection element and fluidically coupled or capable of coupling to a channel outlet via a second channel intersection element, and wherein the filter chamber can be fluidically separated from the remainder of the channel system by at least two filter valves. Furthermore, the processing device comprises a pumping mechanism disposed in the pumping branch for establishing a fluid flow in the channel system, wherein the pumping mechanism preferably comprises at least one pumping valve and at least one pumping chamber, and wherein the pumping branch is fluidically coupled or capable of coupling to the channel inlet via a different connection of the first channel intersection element than the filter branch, and fluidically coupled or capable of coupling to the channel outlet via a different connection of the second channel intersection element than the filter branch. In a preferred embodiment, the first channel intersection element and / or the second channel intersection element can be T-shaped. In other words, the channel intersection element can fluidically connect three channels at a common point. As an alternative, a cross-shaped design of the first and / or second channel intersection element is also possible, that is, four channels can be fluidically connected at a point, or in other words, two channels can intersect at a point and be fluidically connected at this point.

[0006] The microfluidic processing device has the following advantages, namely: on the one hand, the filter branch can be flushed or used to extract components from the sample when the filter valve is opened, in particular through the channel inlet and the channel outlet, and on the other hand, the pumping branch can also be flushed when the filter valve is closed, in particular also through the channel inlet and the channel outlet. In addition, preferably when using a pumping mechanism arranged in the pumping branch, a common flushing can be advantageously performed through the filter branch and the parallel pumping branch. It is also particularly advantageous here that the common flushing can be performed as an annular flushing through the filter branch and the pumping branch via the channel intersection element. In this way, for example, extraction, that is, enrichment of components of the sample present in the sample on the filter element, or elution, that is, separation of sample components previously enriched on the filter element, can be performed.

[0007] The processing device of described microfluid can be advantageously used for flushing, especially cleaning filter element, sample purification or extracting component or elution from sample on filter element, namely make sample component break away from filter element, particularly for on filter element or from filter element nucleic acid is purified and eluted.Here, can especially flush with the binding buffer, wash buffer or elution buffer that are used for the purification of sample.The scheme introduced thus also comprises a kind of method for the processing device of operation microfluid.Preferably can carry out described flushing as mentioned above by channel inlet, filter element and channel outlet, namely advantageously by the shorter path with less potential dead volume, particularly for cleaning or washing of filter element.Preferably do not have flushing fluid or especially in the elution that follows immediately thereafter, flushing fluid as little as possible enters in described pumping branch, this can be by using one or more pumping valves in pumping branch or at channel intersection element place to be supported with pumping branch being separated, wherein said pumping branch for example has the volume that is small compared with this pumping branch. At the filter element, for the purification of the sample, that is, especially at the filter element, extracting the component from the sample can also preferably be carried out through the channel inlet, filter element and channel outlet, wherein preferably no flushing fluid or as little flushing fluid as possible enters the pumping branch. As an alternative, the sample can be flushed once or multiple times via the pumping branch through the filter branch through the filter element by annular flushing, which supports effective purification. Subsequently, as already explained, the filter element can be flushed with a wash buffer. It is preferably possible to elute the sample component, especially nucleic acid, from the filter element when using a pumping branch, preferably when using a pumping mechanism. This is especially advantageous, that is: in the pumping branch, the sample component isolated by the filter element is to be further processed or analyzed, such as, in one or more of the preferably temperature-adjustable pumping mechanisms or pumping chambers in the pumping branch, nucleic acid replication is carried out by polymerase chain reaction or isothermal amplification.

[0008] For example, the processing device can have a size of 30×30 mm. 2 Up to 300×300mm 2 , preferably 50×50mm 2 Up to 100×100mm 2lateral dimensions. The processing device can be, for example, a polymer cartridge with active or actuatable microfluidic elements, that is, microfluidic valves and pumping chambers, each of which can cause the liquid to be discharged from a component of the liquid-conducting structure of the processing device provided for this purpose. For example, the valves and pumping chambers can be pneumatically controlled by a processing unit provided for this purpose, thereby enabling fully automated microfluidic processing of the liquid in the polymer cartridge. The valves and pumping chambers can be implemented or covered by at least one flexible diaphragm, which can be adjacent to other polymer components, at least one of which can contain a liquid-conducting microfluidic structure. The microfluidic valve can be implemented by separating the two liquid-conducting structures through a pneumatically induced deflection of the diaphragm in a subspace provided for this purpose and advantageously shaped toward the liquid-conducting microfluidic structure. The microfluidic pumping chamber can also be based on the discharge of liquid from a region of the liquid-conducting structure of the processing device provided for this purpose, similar to a valve. In contrast to a valve, a pumping chamber can have, for example, a larger volume than a valve and serve, for example, to temporarily receive a defined amount of liquid, in particular a substantial part or almost the entire amount of liquid to be processed in a microfluidic process step.

[0009] For example, a microfluidic pumping chamber can advantageously be used in combination with two microfluidic valves surrounding the pumping chamber to create a pumping mechanism, also referred to as a pumping unit, that can achieve the highest possible flow rate in a microfluidic processing device using the most compact space possible. This can be achieved, for example, by constructing the pumping mechanism from a pumping chamber with a large displacement and two valves with smaller displacements, wherein the pumping chamber is used for pumping, i.e., for the directed discharge of the liquid, and the valves are used solely for determining and establishing the pumping direction via a suitable actuation pattern. Advantageously, such a pumping mechanism can be distinguished by a large pumping volume per pumping step and by a small space requirement for achieving the pumping unit, as well as a pulsating, i.e., unstable, flow rate profile that varies greatly over time.

[0010] In order to bring about a pumping process with a flow rate that is as constant as possible and less variable, peristaltic pumping is provided, for example, by peristaltic actuation of at least three active microfluidic elements of the same type, wherein the at least three active microfluidic elements can have similar volumes and have almost the same volumes. Peristaltic pumping with three active microfluidic elements of the same type can be achieved independently of their identical displacements, that is, not only by using microfluidic valves that can have a small displacement but also by using microfluidic pumping chambers that can have a larger displacement. Therefore, with regard to peristaltic liquid transport, the conceptual distinction between "valve" and "pumping chamber" is invalid. Only when there is a multifunctional use of the microfluidic elements, as in the variant of the processing device presented here, does the conceptual distinction make sense, i.e. there are microfluidic elements that, in addition to establishing peristaltic liquid transport, are primarily used to control the microfluidic flow within the microfluidic processing device, and are therefore referred to as microfluidic valves below. There are microfluidic elements that, in addition to establishing peristaltic liquid transport, are primarily used to generate microfluidic flows and to temporarily store a significant portion of the liquid volume to be processed within the microfluidic device. These are therefore referred to below as microfluidic pumping chambers. Depending on the function used, the microfluidic element is advantageously designed: microfluidic valves, and in particular microfluidic control valves or isolating valves, i.e., microfluidic valves that are used solely for controlling the microfluidic flow or for isolating liquid-conducting structures and not for peristaltic liquid transport, therefore have a particularly small displacement volume, specifically, on the one hand, to minimize the amount of liquid that can be flushed during the microfluidic process, and on the other hand, to achieve the most compact design possible for the microfluidic device. Pumping chambers, in particular, which can be used for storing and measuring liquids in a defined manner, in contrast, have a predetermined displacement volume, for example, 20 μl, which corresponds substantially to the liquid volume to be processed, or at least to a significant portion thereof.

[0011] In the processing device described here, the filter chamber arranged in the filter branch is designed to accommodate a filter element, which can also be referred to as a filter. Here, the filter chamber can have a volume of, for example, 3 μl to 20 μl, preferably 5 μl to 10 μl, and is surrounded by two filter valves with a displacement of, for example, 80 nl to 1 μl, preferably 100 nl to 300 nl. This advantageously creates the smallest possible volume for the filter branch, thereby enabling particularly efficient microfluidic processing, particularly for purifying sample liquids.

[0012] The filter element can be, for example, a silica filter that can be used to extract nucleic acids. For example, different buffer solutions can be pumped through the filter element when using the processing device, so as to achieve the binding of nucleic acids to the silica filter with a so-called binding buffer, or to achieve the separation of nucleic acids bound to the silica filter with a so-called elution buffer, or to cause the silica filter to be rinsed with a so-called wash buffer between the binding and separation of the nucleic acids. Here, the processing device advantageously allows the microfluidic processing for purifying the sample liquid when using a filter element with only a small dead center amount. The sample liquid can be, for example, an aqueous solution having a sample material contained therein, in particular a sample material derived from a human, such as obtained from a body fluid, smear, secretion, sputum or tissue sample. The index to be detected in the sample liquid is particularly of medical, clinical, therapeutic or diagnostic significance and can be, for example, bacteria, viruses, specific cells, such as circulating tumor cells, cell-free DNA or other biomarkers.

[0013] For example, by the variant of the microfluidic processing device introduced here, the amount of wash buffer that may undesirably enter the elution buffer can be reduced. In this way, particularly high efficiency can be achieved when purifying the sample liquid.

[0014] Since, in addition to the properties of the filter element, the chemical composition of the buffer solution used and the properties of the sample liquid and the components to be extracted, the manner and method of processing the microfluidic system play a decisive role in the extraction efficiency, the processing device described here is advantageously designed to achieve particularly effective purification of the sample or sample liquid. To this end, the channel system, which can also be referred to as a channel, can be formed, for example, in the form of a ring or a loop, wherein the filter chamber arranged in the channel system, the at least one pumping chamber and the different valves are fluidically coupled or can be coupled to the channel system. In this case, the first channel intersection element arranged in the channel system is preferably T-shaped, wherein the channel inlet, the filter branch and the pumping branch are each connected to another connection of the first channel intersection element and are thereby coupled or can be coupled to each other. In the same way, the second channel intersection element is also preferably T-shaped and forms a connection between the channel outlet, the filter branch and the pumping branch, which are also each connected to another connection of the second channel intersection element. The cross-sectional area of ​​the microfluidic channel in the channel system and the cross-sectional area of ​​the connection point to the channel system can be, for example, 0.2×0.2 mm 2 Up to 2×2mm 2 , preferably 0.3×0.3mm 2 Up to 0.8×0.8mm2 .

[0015] The processing device can advantageously be manufactured cost-effectively from a polymer material such as polycarbonate (PC), polypropylene (PP), polyethylene (PE), cycloolefin copolymer (COP, COC), or polymethyl methacrylate (PMMA), for example, using high-throughput technologies such as injection molding, thermoforming, or stamping, wherein the processing device can be produced, for example, by means of laser transmission welding. Liquid transport within the microfluidic processing device can be achieved in a particularly simple manner by deflecting a flexible polymer membrane into a fluid-conducting cavity of a rigid polymer component, making it possible to controllably discharge the liquid within the microfluidic processing device by applying different pressure levels to the pneumatic interface of the processing device. For example, a thermoplastic elastomer (TPE), such as polyurethane (TPU) or styrene block copolymer (TPS), can be used as the flexible membrane. Microstructuring of the flexible membrane can be performed, for example, by stamping. The liquids that can be used in the treatment device can be, for example, aqueous solutions or buffer solutions, as well as fluorinated hydrocarbons such as 3M Fluorinert inert liquid for sealing microcavities, and also oils such as mineral oil, paraffin oil, or silicone oil for producing multiphase systems in the treatment device. The liquids can be introduced, for example, poured into the treatment device during its manufacture and enclosed in a reagent plug, which allows, for example, long-term stable storage of the liquid in the treatment device.

[0016] According to one embodiment, the pumping mechanism can include two, in particular three, pumping chambers arranged or connected adjacent to each other in a series. For example, it can involve three pumping chambers of the same type, arranged in a series on the microfluidic channel, which can also be referred to as chambers. The pumping chambers can, for example, be used to establish a flow in a channel system and in particular through a filter chamber and can be constructed to accommodate a limited amount of liquid. Here, the pumping chamber can be separated from the channel system by two pumping valves that surround two of the three pumping chambers. Advantageously, the limited amount of liquid can be pumped back and forth within the interior of the three pumping chambers, including within the connecting channels between the chambers, without exchanging liquid with the rest of the microfluidic network. In addition, by suitably controlled actuation of the two or three pumping chambers, liquid transport through the microfluidic channel system and in particular through the filter chamber can be achieved, wherein the amount of liquid transported in the pumping step can correspond to the displacement of the pumping chamber. Depending on the selected actuation mode, liquid transport in the microfluidic channel system can be carried out unidirectionally or bidirectionally.

[0017] According to another embodiment, described pumping mechanism can comprise another pumping chamber, wherein said another pumping chamber can be separated or can be separated from the pumping chamber that is connected in series by at least one pumping valve.Such as, described another pumping chamber can be connected in series with the rest of the pumping chambers of pumping mechanism, wherein said another pumping chamber can be separated from the channel system by the pumping valve of two microfluids for example.Advantageously, described another pumping chamber can be used to carry out optimized liquid transportation in microfluidic channel system in conjunction with other pumping chambers, wherein said amount of liquid carried in the pumping step can be corresponding to the displacement of two pumping chambers.In this way, such as can realize pumping by means of four pumping chambers within the scope of elution step, wherein the amount of liquid processed of elution buffer can be corresponding to the displacement of two pumping chambers basically.Immediately after elution, then such as can be for implementing the reagent of polymerase chain reaction and eluate dissolving and in three pumping chambers that separate by two valves and pass through respectively suitable temperature-regulated, implement amplification reaction, wherein in polymerase chain reaction, employed amount of liquid can be corresponding to the displacement of a pumping chamber basically. Subsequently, dilution and / or the addition of further reagents can be achieved so that the amount of liquid can again essentially correspond to the displacement of the two pumping chambers. Overall, this embodiment has the advantage that a high flexibility can be achieved when implementing, for example, microfluidic processes for implementing molecular diagnostic tests.

[0018] Advantageously, different pumping rates and flow rate profiles are provided. By optimizing the pumping rate, in particular the pumping rate for the treatment of the filter element or the liquid flow flowing through the filter element, the efficiency of the purification can be improved. In particular, an optimized pumping protocol for microfluidic treatment can be determined and used based on the composition of the filter material and buffer solution used. Particularly low flow rates can reduce shear forces acting on components present in the sample liquid, for example.

[0019] According to another embodiment, each of the series-connected pumping chambers can have substantially the same volume as the other pumping chamber. For example, the displacement of a pumping chamber can be 10 μl to 50 μl, in particular 15 μl to 25 μl. The pumping chambers can each have the same volume, for example, within a tolerance range of 5%. Unlike the pumping chambers, the pumping valve of the pumping mechanism can have a displacement of, for example, 200 nl to 3 μl, in particular 500 nl to 2 μl. Advantageously, the peristaltic pumping process can be facilitated by suitably controlled actuation of the pumping chambers, wherein the amount of liquid transported in the pumping step can correspond to the displacement of a pumping chamber.

[0020] Advantageously, the processing device allows for microfluidic processing of variable liquid quantities. By combining a pumping valve and a pumping chamber, i.e., a flow-generating microfluidic element with at least two different displacements, it is possible, for example, to not only precisely transport particularly small, precisely defined liquid quantities at low flow rates using a pumping valve, but also to rapidly transport large liquid quantities at higher flow rates using at least one pumping chamber. In this way, the processing device presented here can be advantageously used in a particularly versatile and universal manner.

[0021] According to another embodiment, at least two of the series-connected pumping chambers can each be designed to be independently temperature-controlled. For example, the pumping chambers can be brought to different temperatures essentially independently of one another by means of a temperature control mechanism. For example, the first of three series-connected pumping chambers can be brought to a temperature between approximately 94 and 96°C, for example, 95°C; the second can be brought to a temperature between 68 and 72°C, for example, 70°C; and the third can be brought to a temperature between 55 and 65°C, for example, 60°C. This advantageously allows, for example, a polymerase chain reaction to be carried out by pumping back and forth between the differently temperature-controlled pumping chambers, using liquid quantities separated by pumping valves and essentially predetermined by the size of the pumping chambers.

[0022] According to another embodiment, the processing device can have a channel system expansion module that is coupled or can be coupled to the pumping branch fluidly, wherein the channel system expansion module can include at least one pre-storage chamber for pre-storing reagents and as a supplementary solution or alternative solution, include at least one evaluation chamber with an evaluation cavity for evaluating the sample components of the sample liquid. When an external analytical device is used to analyze the evaluation cavity, an evaluation signal can be provided when using the processing device introduced here. For example, the pre-storage chamber can be used for pre-storing dry reagents. In this way, for example, a lyophilized material can be pre-stored in this pre-storage chamber, and the lyophilized material can also be called beads (Bead) and the lyophilized material is configured to prepare a reaction liquid or a reaction mixture, such as for implementing a polymerase chain reaction. For example, immediately after the purification of the sample, the dry reagent can be dissolved by at least a portion of the eluate obtained to prepare a reaction liquid, which contains the sample material purified by means of a filter element and can then be used, for example, in the case of using the arrangement structure composed of the pumping chamber described above, for the amplification of the components of the sample material, such as, for example, a specific DNA sequence, so that, for example, fluorescence or chemiluminescence-based detection of these components of the sample material can be achieved subsequently. Here, the evaluation chamber can, for example, include a chip with an array composed of microcavities and constitute a flow cell (Flusszelle) for microfluidic processing of the chip with microcavities. The so-called array chip can, for example, be essentially composed of silicon, made of a silicon plate ("silicon wafer") by photolithography, etching, coating and separation. In the microcavity, for example, reagents specific to indicators can be pre-stored, which can, for example, be used to detect different indicators in the liquid by geometric multiplexing, wherein the reagents can, for example, be introduced into the microcavity by means of a fine dispersion system. Therefore, it is advantageous to study the sample liquid in terms of a variety of different characteristics when using a channel system expansion module.

[0023] According to another embodiment, the pre-storage chamber can be fluidically coupled or can be coupled to the pumping branch via a channel connecting element that can be closed with a pre-storage valve, and the evaluation chamber can be fluidically coupled or can be coupled to the pumping branch via another channel connecting element that can be closed with an evaluation valve. For example, the pre-storage valve and the evaluation valve can be closed while the sample liquid is being processed within the pumping branch. This advantageously allows the flow to be restricted to the area of ​​the channel system that is necessary for the process.

[0024] According to another embodiment, the pumping mechanism can include a single pumping chamber and at least three pumping valves. For example, the three pumping valves can be actuated independently of one another and, by actuation according to a peristaltic pattern, used to establish a flow in the microfluidic channel system, and in particular in the filtration chamber. This advantageously allows the pumping mechanism to be designed in a particularly space-saving manner.

[0025] According to another embodiment, an inlet valve can be arranged between the channel inlet and the first channel intersection element, and an outlet valve can be arranged additionally or alternatively between the channel outlet and the second channel intersection element. For example, the use of both inlet and outlet valves can separate the channel inlet and channel outlet of a microfluidic system, which is designed, for example, in a loop, including the filter chamber with the filter element, from the rest of the microfluidic network. This advantageously enables in-loop pumping within the microfluidic channel system, bypassing the filter chamber without exchanging liquids with the rest of the microfluidic network.

[0026] In addition, also as mentioned above, introduce a method for a variant of the processing device for running the microfluid described above. Here, the method comprises the steps of introducing the sample liquid into the processing device of the microfluid, extracting or purifying the sample components present in the sample liquid by a filter element, and eluting the sample components from the filter element. "Elution" can refer to the separation of the sample components from the filter element. With such an embodiment of the scheme introduced here, the advantages mentioned above can be easily and cost-effectively achieved technically.

[0027] According to one embodiment, the method can include an additional step of lysing components of the sample liquid immediately after the introduction step and before the extraction step, and, in addition or as an alternative, a step of washing the filter element and, as an alternative or in addition, washing the filter chamber immediately after the extraction step and before the elution step. This embodiment can significantly improve the analysis of the sample liquid.

[0028] In addition, described method can comprise and immediately after the elution step, provide the additional step of reaction liquid by means of the dissolving of reagent when using sample component.As supplementary scheme or alternative, described method can have the additional step of implementing amplification reaction, and as supplementary scheme or alternative, can have the additional step of dividing reaction liquid into equal parts, and as supplementary scheme or alternative, can have the additional step of implementing detection reaction, and as supplementary scheme or alternative, can have the additional step of evaluating reaction product.Through such embodiment, also can realize the obvious improvement for the analysis of described sample liquid.

[0029] Such a method can be implemented, for example, in the form of software or hardware or in a hybrid form of software and hardware, for example in a control unit.

[0030] Furthermore, the solution presented here provides a control device that is designed to implement, control, or realize the steps of a variant of the method presented here in corresponding mechanisms or units. This embodiment variant of the invention in the form of a control device allows the object of the invention to be achieved quickly and effectively.

[0031] To this end, the control device can include at least one computing unit for processing signals or data, at least one memory unit for storing signals or data, at least one interface to a sensor or actuator for reading in sensor signals from the sensor or for outputting control signals to the 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 memory unit can be a flash memory, an EEPROM, or a magnetic storage unit. The communication interface can be designed to read in or output data wirelessly and / or wired, wherein a communication interface capable of reading in or outputting wired data can, for example, read in this data from a corresponding data transmission line electrically or optically or output this data to a corresponding data transmission line.

[0032] A "controller" in this context may refer to an electrical device that processes sensor signals and outputs control and / or data signals accordingly. The control device may have an interface that can be implemented in hardware and / or software. In a hardware implementation, the interface may, for example, be part of a so-called system ASIC that contains the various functions of the control device. However, it is also possible for the interface to be a separate integrated circuit or to be at least partially composed of discrete components. In a software implementation, the interface may be a software module that is located, for example, on a microcontroller alongside other software modules.

[0033] 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, for example, 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 implement, realize and / or control the steps of the method according to one of the embodiments described above. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] An exemplary embodiment of the solution presented here is shown in the drawings and explained in detail in the following description.

[0035] Figure 1 A schematic diagram showing an embodiment of a processing device;

[0036] Figure 2 shows a schematic top view of an embodiment of a processing device;

[0037] Figure 3 A schematic diagram showing an embodiment of a processing device having a channel system expansion module;

[0038] Figure 4 shows a schematic top view of an embodiment of a processing device having a channel system expansion module;

[0039] Figure 5A A flow chart illustrating an embodiment of a method for operating a microfluidic processing device;

[0040] Figure 5B Shows a block diagram of a control device for operating a microfluidic processing device according to the variant presented here;

[0041] Figure 6 A flow chart showing an embodiment of a method for operating a microfluidic processing device, the method having an additional lysis step and an additional wash step; and

[0042] Figure 7 A flow chart showing an embodiment of a method for operating a microfluidic processing device having a channel system expansion module. DETAILED DESCRIPTION

[0043] In the following description of advantageous embodiments of the present invention, identical or similar reference numerals are used for similarly functioning elements shown in different figures, with repeated descriptions of these elements omitted. If an embodiment includes an "and / or" connection between a first feature and a second feature, this is to be interpreted as follows: the embodiment includes both the first feature and the second feature according to one embodiment and either only the first feature or only the second feature according to another embodiment.

[0044] Figure 1 FIG. 1 is a schematic diagram of an embodiment of a processing device 100. In this embodiment, the processing device 100 is a 45×25 mm 2 The processing device 100 in this embodiment comprises a microfluidic channel system 105 for receiving the sample liquid, that is, the liquid having components of the sample. The cross-sectional area of ​​the channel system 105 in this embodiment is 0.4×0.6 mm 2 In another embodiment, the channel system is 0.8×0.8 mm 2The cross-sectional area of ​​the processing device 100 is shaped. In this embodiment, the sample liquid is introduced into the processing device 100 via a channel inlet 110, which forms a connection point with the microfluidic network (not shown in this figure). The channel inlet 110 can be separated from the rest of the processing device 100 by means of an inlet valve 115. In this embodiment, the inlet valve 115 is arranged between the channel inlet 110 and a first channel intersection 120, which is preferably T-shaped. While the channel inlet 110 is fluidically coupled to a connection of the first channel intersection 120 via the isolating valve 115, the other connection of the first channel intersection 120 is fluidically coupled to a filter branch 125 of the processing device 100. The filter branch 125 includes a filter chamber 130, in which, in this embodiment, a filter element 135 is arranged. The filter chamber 130 can be used to extract sample components, which can also be referred to as sample components. A first filter valve 140a is arranged between the filter chamber 130 and the first channel intersection 125. Furthermore, a second filter valve 140b is arranged between the filter chamber 130 and the second channel intersection 145. The first and second filter valves 140a, 140b allow the filter chamber 130 to be separated from the rest of the processing device 100. In other words, the two filter valves 140a, 140b, which can also be referred to as microfluidic on / off valves, are arranged on either side of the filter chamber 130 in the immediate vicinity of the microfluidic channel. Closing the two filter valves 140a, 140b allows the filter chamber 130 to be separated from the channel. In this embodiment, the filter valves 140a, 140b have a particularly small volume to minimize the space surrounding the filter chamber 130. The filter valves 140a, 140b are merely connected in series as an example, so that they can be actuated jointly via a single pneumatic control channel.

[0045] The processing device 100 is therefore distinguished by a particularly advantageous arrangement and design of microfluidic elements for filter-based purification of a sample liquid, in particular by the realization of a microfluidic channel system 105 that is designed, in particular, in a loop-shaped manner and includes a filter chamber 130 with a filter element 135, wherein the filter chamber 130 can be separated in a fluid-tight manner from the rest of the microfluidic channel system 105 by two microfluidic filter valves 140a, 140b. In this case, the two microfluidic filter valves 140a, 140b are actuated in particular together to achieve a particularly simple and compactly implementable pneumatic actuation. In addition, the processing device 100 has two preferably T-shaped channel intersection elements 120, 145, which are arranged in the closest possible environment to the two filter valves 140a, 140b that surround the filter chamber 130 and can also be called separation valves and form exactly two microfluidic connection points with the microfluidic channel system 105, so that the rest of the microfluidic channel system 105 can be flushed through the connection points, especially when the filter valves 140a, 140b that surround the filter chamber 130 are closed.

[0046] When the second filter valve 140b is open, the filter chamber 130 is fluidically coupled via the connection of the T-shaped second channel intersection 145 to a channel outlet 150 connected to another connection of the second channel intersection 145. In this embodiment, the channel outlet 150 forms a connection point with a capture chamber (not shown in the figures), wherein the channel outlet 150 can be used to discharge the sample liquid after the components have been extracted through the filter element 135. Here, the channel outlet 150, like the channel inlet 110, can be separated from the rest of the processing device 100 by an outlet valve 152. Both the first channel intersection 120 and the second channel intersection 145 can also be referred to as channel intersections, and accordingly, they surround the filter chamber 130 and the two filter valves 140a, 140b, which can also be referred to as on / off valves, arranged around the filter chamber 130. This minimizes the volume of the filter branch 125, thereby enabling particularly efficient microfluidic processing, particularly with regard to sample liquid purification.

[0047] The pumping branch 155 with a pumping mechanism 157 is connected in parallel with the filtering branch 125, wherein the pumping branch 155 is coupled to the channel inlet 110 fluidically by a different joint of the first channel intersection element 120 than the filtering branch 125 and is coupled to the channel outlet 150 fluidically by a different joint of the second channel intersection element 145 than the filtering branch 125. In the present embodiment, the filtering branch 125 and the pumping branch 155 form a loop-shaped closed system by passing through the connection of the channel system 105. In the present embodiment, the pumping branch 155 has at least two, here just three pumping chambers 160a, 160b, 160c, which are directly adjacent to each other. The pumping chambers 160a, 160b, 160c are arranged in series along the microfluidic channel system 105 in the present embodiment and are thus connected in series and have almost the same volume. Merely by way of example, they can be fluidically separated from the remaining areas of the treatment device 100 by two microfluidic pumping valves 165 a , 165 b which enclose the three pumping chambers 160 a , 160 b , 160 c .

[0048] The described arrangement structure of the string shape that is made of pumping chamber 160a, 160b, 160c and pumping valve 165a, 165b on the microfluidic channel system 105 of loop shape can realize peristaltic pumping process, and it can be used for by filter chamber 130 and in the inside of microfluidic channel system 105, carry liquid.At this, described pumping chamber 160a, 160b, 160c can also individually, namely basically independently of one another temperature control in the present embodiment.In this way, described three pumping chambers 160a, 160b, 160c can be used to for example implement polymerase chain reaction in the scope that sample liquid is purified except controlled ground admits sample liquid and in channel system 105, produces microfluid stream especially in using filter chamber 130 with filter element 135.Just after the purification of described sample liquid, described pumping chamber 160a, 160b, 160c can therefore equally realize the amplification of the sample material purified in treatment unit 100.

[0049] On the other hand, this embodiment has a further pumping chamber 170, wherein each of the serially connected pumping chambers 160a, 160b, 160c has substantially the same volume as the further pumping chamber 170, so that a total of four identical pumping chambers 160a, 160b, 160c, 170 are present. This allows for particularly flexible handling of liquid quantities that substantially correspond to the displacements of up to two of the pumping chambers 160a, 160b, 160c, 170, thereby enabling advantageous execution of different steps of a test process within the processing device 100. In this embodiment, the further pumping chamber 170 can also be separated from the remaining areas of the processing device 100 by two further pumping valves 175a, 175b. Here, not only the pumping valves 165a, 165b but also the further pumping valves 175a, 175b are designed as peristaltic pumping valves in addition to their separation function, and therefore have a larger displacement than the first filter valve 140a and the second filter valve 140b, which are primarily constructed to separate the filter chamber 130 from the rest of the treatment device 100.

[0050] Figure 2 A schematic top view of an embodiment of a processing device 100 is shown. Figure 1 The processing device depicted in .

[0051] In this embodiment, the processing device 100 is based on a flexible, microstructured polymer membrane that has been welded, in particular partially over a wide area, to two microstructured polymer components by means of laser welding, which can also be referred to as laser transmission welding. Liquid-conducting recesses are present in the rigid polymer components, forming the microfluidic channels of the channel system 105, the pumping chambers 160a, 160b, 160c, the further pumping chamber 170, the pumping valves 165a, 165b, the further pumping valves 175a, 175b, the filter valves 140a, 140b, the inlet valve 115, and the outlet valve 152. Furthermore, at least one of the components has, in particular, a pneumatic channel 210 for actuating active microfluidic elements, in particular pumping chambers and valves. In this embodiment, the microfluidic elements are actuated by a pressure-dependent, locally defined deflection of the elastic membrane into the recesses of the polymer components that form the valves and pumping chambers. At least two pressure levels are used to control the microfluidic elements. In particular, the pressure levels are controlled and provided via an external processing unit that has a pneumatic interface 205 with the processing device 100. For exemplary purposes only, the interface 205 is arranged at the left edge of the illustration in this figure. The pneumatic channels 210 for controlling the microfluidic elements are shown in red in this figure. The microfluidic channels of the channel system 105 and the filter chamber 130 are shown in blue, and the pneumatically controllable microfluidic elements, like the pneumatic channels 210, are shown in red.

[0052] Figure 3 The schematic diagram shows an exemplary embodiment of a treatment device 100 having a channel system expansion module 300. This can be the treatment device depicted in the preceding figures.

[0053] In this embodiment, the series of pumping chambers 160a, 160b, and 160c can be temperature-controlled independently of one another using a temperature control mechanism (not shown). For example only, the first pumping chamber 160a of the three pumping chambers is maintained at 95°C, the second pumping chamber 160b is maintained at 70°C, and the third pumping chamber 160c is maintained at 60°C. This allows for a polymerase chain reaction to be performed within the volume of liquid periodically pumped back and forth between the three pumping chambers 160a, 160b, and 160c. In this embodiment, the series of pumping chambers 160a, 160b, and 160c can be separated from the microfluidic channel system 105 by two microfluidic pumping valves 165a and 165b. In this way, liquid plugs (Flüssigkeits-Plugs) can be pumped back and forth and temperature-controlled particularly effectively in the three pumping chambers 160a, 160b, 160c, wherein liquid losses are prevented by separating the unit consisting of the three pumping chambers 160a, 160b, 160c with the help of microfluidic pumping valves 165a, 165b and minimizing the dead volume adjacent to the pumping chambers 160a, 160b, 160c during thermal and microfluidic processing of the liquid quantity.

[0054] In the present embodiment, the pumping branch 155 is fluidically coupled to the pre-storage chamber 310 via an additional, preferably T-shaped, channel intersection element 305. Merely by way of example, the pre-storage chamber 310 is used for pre-storing lyophilized reagents. Between the additional channel intersection element 305 and the pre-storage chamber 310, a pre-storage valve 320 is arranged at the channel connecting element 315, wherein the pre-storage valve 320 is constructed to separate the pre-storage chamber 310 from the pumping branch 155. Thus, in the present embodiment, the channel connecting element 315 establishes a connection between the pumping branch 155 and the microfluidic pre-storage chamber 310, which can be closed by the pre-storage valve 320, and the microfluidic pre-storage chamber comprises at least one pre-stored reagent 318, in particular so-called beads, which can also be referred to as lyophilisates and which can be used to provide a reaction liquid when using an eluate, i.e., a liquid, which is used in the treatment device 100 and in Figure 1 In the case of the filter element 135 depicted in FIG, the sample liquid is obtained from the purification process. In other words, the reaction liquid, which can also be referred to as a reaction mixture, is provided by dissolving the beads in a microfluidic pre-storage chamber 310 using the eluate previously obtained from the purification process. The pre-storage chamber 310 is pneumatically actuable only as an example and is therefore similar to the other pumping chambers 160a, 160b, 160c in that the pre-storage chamber 310 also provides a pumping action.

[0055] In the present embodiment, the microfluidic channel system 105 has another preferably T-shaped channel intersection element 325 between the additional channel intersection element 305 and another pumping valve 175a, and the channel intersection element has another further extended channel connecting element 327, through which the pumping branch 155 is fluidically coupled to the evaluation chamber 330. Here, the other channel connecting element 327 can be closed with an evaluation valve 335. The evaluation chamber 330, which can also be called an array chamber, includes a chip in the present embodiment, which has an array of evaluation cavities 345, which can also be called microcavities. In the evaluation cavity 345, only reagents specific to the indicators are pre-stored as an example, and the reagents can be used to detect different indicators in the liquid through geometric multiplexing. In this way, when using the channel system expansion module 300, a variety of different characteristics of the sample can be studied. The microfluidic valve 347a, 347b that is particularly provided with for the processing of microfluidic by means of peristaltic pumping to evaluation chamber 330 only has the displacement that is suitably designed for this purpose by way of example.In the present embodiment, the displacement of the microfluidic valve 347a, 347b exceeds the volume of the pumping valve 165a, 165b that is used for carrying out peristaltic pumping in pumping branch 155.In this way, higher flow rate can be produced with the valve 347a, 347b, while the pumping valve 165a, 165b then has less position space requirement and therefore allows to realize the device as compactly as possible.In addition, the present embodiment additionally comprises the inlet leading to another pre-storage chamber 350 that can also be called bead chamber, in which there is another kind of freeze-dried reagent 358, which only can be used for preparing the reaction liquid for multiple detection in the chip with evaluation cavity 345 by way of example. In other words, this embodiment includes additional microfluidic elements that are particularly useful for conducting in-depth sample analysis of sample material purified using the processing device 100. In addition to the integration of additional chambers for pre-storing additional dry reagents, such as those used to perform additional detection and / or amplification reactions, the processing device 100, in this embodiment, includes a unit for aliquoting or separating the processed sample liquid. Advantageously, different independent detection reactions can be performed to address different indicators in the sample liquid by pre-storing additional dry reagents in the evaluation cavity 345 for aliquoting into individual aliquots. This approach, which can also be referred to as geometric multiplexing, allows the sample liquid to be studied for the presence of a variety of different characteristics. In another embodiment, the chip with the evaluation cavity 345 allows for microfluidic generation of a particularly large number of aliquots of the processed sample liquid, particularly small amounts exceeding 1,000. In this way, digital sample analysis can be achieved.In this way, for example, the number of copies of a variable initially present in the sample liquid can be quantified with absolute precision.

[0056] Figure 4 1 shows a schematic top view of an embodiment of a processing device 100 with a channel system expansion module 300. This can be the processing device described in the previous figures and in Figure 3 The channel system expansion module depicted in .

[0057] In this embodiment, the processing device 100 includes a pre-storage chamber 310 , another pre-storage chamber 350 , and an evaluation chamber 330 , which is configured to receive and microfluidically process a chip having an evaluation cavity 345 .

[0058] In this embodiment, the microfluidic processing device 100 is tilted at an angle of about 30° relative to the direction of action of the gravitational field. In another embodiment, the processing device 100 is tilted at an angle of about 30° relative to the direction of action of the gravitational field at a predetermined angle range between 0° and 45° relative to the direction of action of the gravitational field at about 9.81 m / s. 2 In the embodiment of the present invention, the microfluidic channel of the present invention is used for the treatment of the microfluidic cell 100. The ...

[0059] Figure 5A A flow chart of an exemplary embodiment of a method 500 for operating a microfluidic processing device is shown. This can be the processing device depicted in the preceding figures.

[0060] The method 500 includes a step 505 of introducing the sample liquid into a microfluidic processing device. In addition, the method 500 includes a step 510 of extracting the sample components present in the sample liquid through a filter element, wherein the components present in the sample liquid are combined with the filter element in the filter chamber, wherein the components are nucleic acids in this embodiment. In order to improve or to achieve the combination of the components with the filter, this step is only performed, for example, under the condition of pumping a binding buffer. As mentioned above, the extraction and the optional subsequent washing steps of the filter element can be performed through the channel inlet 110, the filter branch 125 and the channel outlet 150, wherein, in particular, no fluid or as little fluid as possible is directed into the pump branch 155 by closing the pump valves 165a, 165b and preferably also when closing other pump valves 175a, 175b. In addition, the method 500 includes a step 515 of eluting the sample components from the filter element. Here, the sample components combined with the filter are loosened. At this can as mentioned above especially when closing inlet valve 115 and outlet valve 152 and when opening pumping valve 165a, 165b and (if existing) preferably other pumping valve 175a, 175b via the flushing that is carried out by pumping branch 155 and filtering branch 125, in special design scheme via repeatedly, annular flushing, carry out described elution.Only exemplary is that this is carried out when using elution buffer, and described component is present in described elution buffer after loosening.In another embodiment, before real elution, with elution buffer, described microfluidic channel is flushed when filter chamber is separated by means of the filter valve of microfluidic, so that remove the residual part in conjunction with buffer and wash buffer.

[0061] Figure 5B A block diagram of an exemplary embodiment of a control device 550 for operating a microfluidic processing device according to the variant described herein is shown. The control device includes a unit 555 for controlling the introduction of a sample liquid into the microfluidic processing device. Furthermore, the control device 550 includes a unit 560 for controlling the extraction of sample components present in the sample liquid through a filter element, and a unit 565 for controlling the elution of sample components from the filter element.

[0062] Figure 6 A flow chart of an exemplary embodiment of a method 500 for operating a microfluidic processing device is shown, which method has an additional lysis step 600 and an additional washing step 605. This can be the method depicted in FIG. 5 .

[0063] In this embodiment, immediately after the introduction step 505 and before the extraction step 510, a step 600 of lysing the sample liquid is performed. In this step, components present in the sample liquid, such as bacteria or cells, are lysed. The lysis is performed, for example, by adding a lysis buffer to the sample liquid. The lysis buffer, mixed with the sample liquid, can then be guided through the channel inlet 110, the filter branch 125, and the channel outlet 150 during the extraction step 510, particularly when the first pumping valve 165a is closed and the other first pumping valve 175a is closed. This allows for the enrichment of sample components released during the lysis, such as nucleic acids, on the filter element. In another embodiment, the lysis is performed by the action of ultrasound. Additionally, in this embodiment, the method 500 includes a step 605 of washing the filter element and filter chamber immediately after the extraction step 510 and before the elution step 515. As described above with respect to FIG. 5 , the washing step 605 can be performed within the relatively short path of the channel inlet 110, the filter branch 125, and the channel outlet 150. In particular, in the washing step 605 , the residues of the binding buffer present in the environment of the filtration chamber are removed and replaced with the washing buffer.

[0064] Figure 7 A flow chart of an exemplary embodiment of a method 500 for operating a microfluidic processing device having a channel system expansion module 300 is shown. This can be shown in FIG. 5 and in FIG. Figure 6 The method described in .

[0065] In this embodiment, the method 500 has an additional step 700 of providing a reaction liquid by dissolving a reagent, using sample components, following the elution step 515. The step 700 of providing a reaction liquid can also be referred to as a bead dissolution step. In this case, at least a portion of the previously obtained eluate is transferred to the bead dissolution step. Figure 3 In order to dissolve the reagents pre-stored therein and prepare the reaction liquid for the first amplification reaction.

[0066] In addition, in this embodiment, method 500 includes step 705 of performing an amplification reaction. Here, the generated reaction liquid is periodically temperature-controlled to two different temperature levels in a processing device, merely as an example, in two pumping chambers arranged in series and separable by pumping valves, in particular in one or more of pumping chambers 160a, 160b, and 160c in pumping branch 155. In this embodiment, this temperature control is used to perform a multiplex polymerase chain reaction.

[0067] In another embodiment, after step 705 of performing the amplification reaction, a step of diluting the reaction liquid containing the reaction product from the amplification reaction is performed.

[0068] Alternatively, in another embodiment, a temperature adjustment step is performed after step 705 of performing the amplification reaction to cause denaturation of the components of the reaction liquid. Alternatively, in another embodiment, a step of adding additional reagents is performed after step 705 of performing the amplification reaction. The additional reagents are present in liquid or solid form, such as lyophilized or freeze-dried form.

[0069] In this embodiment, step 700 of providing the reaction liquid is repeated after step 705 of performing the amplification reaction. Here, a portion of the diluted reaction liquid containing a portion of the reaction product from the first amplification reaction is used to dissolve additional beads in another pre-storage chamber and prepare the reaction liquid for performing the detection reaction.

[0070] Furthermore, the method 500 in this embodiment includes an additional step 710 of dividing the reaction liquid equally. Here, a portion of the reaction liquid from step 700 of providing the reaction liquid is divided into at least two reaction compartments. To produce the reaction compartments, a portion of the liquid is merely exemplarily divided into two reaction compartments. Figure 3 The microcavity is then sealed by introducing another liquid immiscible with the reaction liquid into the evaluation chamber, so that separate microfluidic reaction compartments consisting of portions or aliquots of the reaction liquid are present in the microcavity. In this embodiment, indicator-specific reagents are pre-stored in each microcavity so that the liquids present in aliquots can be studied for the presence of different indicators.

[0071] In this embodiment, the method 500 further comprises a step 715 of carrying out a detection reaction, in particular in the evaluation chamber 330. Here, the detection reaction is merely exemplarily a second amplification reaction, in particular a polymerase chain reaction, wherein the microcavity and the microfluidic reaction compartment located therein are temperature-controlled to enable the further amplification reaction to be carried out therein. In another embodiment, the detection reaction is an isothermal amplification variant.

[0072] In addition, the method 500 in this embodiment includes an additional step 720 of evaluating the reaction products, particularly in the evaluation chamber 330. This evaluation is performed optically, for example, by evaluating the fluorescence signal caused by the probe molecules present in the respective reaction compartments. Based on this signal, the sample liquid can then be investigated for the presence of various indicator substances. In another embodiment, the evaluation step 720 is performed in parallel with the step 715 of performing the detection reaction.

[0073] In other embodiments of the method 500 , individual steps may be performed repeatedly, their order may be swapped, or they may be omitted.

[0074] In other words, the processing device introduced here can be described as follows:

[0075] The treatment device depicted in the preceding figures is distinguished in particular by the adjustable flow rate and particularly high variability of the pumping characteristics for treating the filter element, in particular by the use of at least two different types of active microfluidic elements for generating the flow. That is, the distinguishing features are particularly the membrane-based elements with at least two different fluid displacements, as described in the preceding figures, and in particular suitably dimensioned pumping chambers and pumping valves. Furthermore, the treatment device has a suitable arrangement and number of microfluidic elements, such as to enable peristaltic pumping with at least three elements, in which the amount of liquid transported in one step corresponds to the displacement of one element, or to enable unidirectional or bidirectional pumping, such as when using four identical elements, in which the amount of liquid transported corresponds to the displacement of two elements. Furthermore, the treatment device depicted in the preceding figures can use different actuation procedures of the microfluidic elements with adjustable actuation frequencies and actuation sequences, so as to enable peristaltic pumping or shuttle pumping, in particular bidirectional, in the microfluidic channel and in particular through the filter chamber containing the filter element. Furthermore, the processing device depicted in the preceding figures allows for a particularly advantageous combination of the processing device, which can also be referred to as a purification unit, with a microfluidic network, as well as a particularly space-saving arrangement and efficient and multiple utilization of the microfluidic elements forming the purification unit. This can be achieved in particular by incorporating three pumping chambers arranged in series into the microfluidic channel system, each of which can be separated from the microfluidic channel system and the microfluidic network surrounding the processing device by two valves adjacent to two outer pumping chambers of the three pumping chambers, and each of which can be temperature-controlled individually, that is, essentially independently of one another. In this way, the three isolated pumping chambers can be used with suitable temperature control to periodically expose the liquid plugs therein to different temperatures and, for example, to carry out a polymerase chain reaction in the liquid plugs.

[0076] In addition, the processing device depicted in the previous figures has a small dead volume, in particular a dead volume of washing buffer that enters the elution buffer undesirably, in particular due to the two filter valves that surround the filter chamber with the filter element and the T-shaped channel intersection element adjacent thereto being arranged as close to each other as possible in space and / or minimizing the channel space present there.

[0077] Furthermore, the processing device depicted in the preceding figures is distinguished by its ability to process variable liquid quantities, in particular by the inclusion of a total of four pumping chambers in the purification unit, so that a liquid plug having substantially the displacement of one or two of the pumping chambers can be processed in the purification unit. The possibility of embedding the sample liquid quantity to be processed in an immiscible second liquid phase can also facilitate the processing process.

Claims

1. A microfluidic processing device (100) for processing a sample liquid, wherein the microfluidic processing device (100) has the following characteristics: at least one microfluidic channel system (105), the microfluidic channel system having at least one filtering branch (125) and a pumping branch (155) connected in parallel with the filtering branch (125); at least one filter chamber (130) arranged in the filter branch (125) for receiving a filter element (135), wherein the filter branch (125) is fluidically coupled to the channel inlet (110) via a first channel intersection element (120) and to the channel outlet (150) via a second channel intersection element (145), and wherein the filter chamber (130) is fluidically separable from the rest of the channel system (105) by at least two filter valves (140a, 140b); a pumping mechanism (157) arranged in the pumping branch (155) for establishing a fluid flow in the channel system (105), wherein the pumping mechanism (157) comprises at least one pumping valve (165a) and at least one pumping chamber (160a), and wherein the pumping branch (155) is fluidically coupled to the channel inlet (110) via a different connection of the first channel intersection element (120) than the filtering branch (125) and is fluidically coupled to the channel outlet (150) via a different connection of the second channel intersection element (145) than the filtering branch (125), In contrast to the pumping valve, the pumping chamber can be used to temporarily accommodate a defined amount of liquid.

2. The processing device (100) according to claim 1, wherein the first channel intersection element (120) is T-shaped.

3. The processing device (100) according to claim 1, wherein the second channel intersection element (145) is T-shaped.

4. The processing device (100) according to claim 1, wherein the pumping mechanism (157) includes two pumping chambers (160a, 160b, 160c) arranged or connected in series adjacent to each other.

5. The processing device (100) according to claim 1, wherein the pumping mechanism (157) includes three pumping chambers (160a, 160b, 160c) arranged or connected in series adjacent to each other.

6. The treatment device (100) according to any one of claims 1 to 5, wherein the pumping mechanism (157) comprises a further pumping chamber (170), wherein the further pumping chamber (170) is separated from the pumping chambers (160a, 160b, 160c) connected in series by at least one pumping valve (175a).

7. The processing device (100) according to claim 6, wherein each of the pumping chambers (160a, 160b, 160c) connected in series and the further pumping chamber (170) have substantially the same volume.

8. The processing device (100) according to claim 6, wherein at least two pumping chambers (160a, 160b, 160c) of the pumping chambers connected in series are designed in such a way that the temperature can be adjusted independently of each other.

9. The processing device (100) according to any one of claims 1 to 5, has a channel system expansion module (300) fluidically coupled to the pumping branch (155), wherein the channel system expansion module (300) includes at least one pre-storage chamber (310) for pre-storing reagents and / or at least one evaluation chamber (330) with an evaluation cavity (345) for evaluating sample components of the sample liquid.

10. A processing device (100) according to claim 9, wherein the pre-storage chamber (310) is fluidically coupled to the pumping branch (155) by means of a channel connecting element (315) that can be closed by a pre-storage valve (320), and wherein the evaluation chamber (330) is fluidically coupled to the pumping branch (155) by means of another channel connecting element (327) that can be closed by an evaluation valve (335).

11. The treatment device (100) according to any one of claims 1 to 3, wherein the pumping mechanism (157) comprises a single pumping chamber (160a) and at least three pumping valves (165a, 165b, 175a, 175b).

12. A processing device (100) according to any one of claims 1 to 5, wherein an inlet valve (115) is arranged between the channel inlet (110) and the first channel intersection element (120) and / or an outlet valve (152) is arranged between the channel outlet (150) and the second channel intersection element (145).

13. A method (500) for operating the microfluidic processing device (100) according to any one of claims 1 to 12, wherein the method (500) comprises the following steps: Introducing (505) a sample liquid into the microfluidic processing device (100); extracting (510) sample components present in the sample liquid through a filter element (135); and Sample components are eluted (515) from the filter element (135).

14. The method (500) according to claim 13 comprises an additional step (600) of lysing the sample liquid immediately after the introduction step (505) and before the extraction step (510), and / or an additional step (605) of washing the filter element (135) and the filter chamber (130) immediately after the extraction step (510) and before the elution step (515).

15. The method (500) according to any one of claims 13 or 14, comprises an additional step (700) of providing a reaction liquid by means of dissolution of a reagent using sample components immediately after the elution step (515), and / or an additional step (705) of carrying out an amplification reaction and / or an additional step (710) of dividing the reaction liquid into equal parts and / or an additional step (715) of carrying out a detection reaction and / or an additional step (720) of evaluating the reaction products.

16. A control device (550) configured to execute and / or control the steps (505, 510, 515) of the method (500) according to any one of claims 13 to 15 in corresponding units (555, 560, 565). 17 . A computer program product comprising a computer program configured to execute and / or control the steps of the method ( 500 ) according to claim 13 .

18. A machine-readable storage medium on which a computer program is stored, which is designed to execute and / or control the steps of the method (500) according to any one of claims 13 to 15.

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