Microfluidic device, method and device for operating a microfluidic device

Abstract

The invention relates to a microfluidic device (100) for processing a liquid. The microfluidic device (100) has a channel (50), a first branch channel (555), a first sealing element (31), a second branch channel (525), a second sealing element (32), and at least one resistance element (20). A first channel branch (550) is connected to the first branch channel (555) for fluidic connection of the channel (50). The first sealing element (31) has a first valve (31a) and preferably a second valve (31b), wherein the first sealing element (31) is arranged between the first channel branch (550) and the first branch channel (555). A second channel branch (520) is connected to the second branch channel (525) for fluidic connection of the channel (50).The second sealing element (32a) has a further valve (32), wherein the second sealing element (32a) is arranged between the second channel branch (520) and the second branch channel (525). The resistance element (20) is arranged on or in the channel (50) and between the first channel branch (550) and the second channel branch (520) and between the first sealing element (31) and the second sealing element (32), wherein the first sealing element (31) can have a greater fluidic resistance than the second sealing element (32).

Description

State of the art

[0001] The invention relates to a microfluidic device, a method, and a device for operating a microfluidic device according to the preamble of the independent claims. The present invention also relates to a computer program.

[0002] Microfluidic devices are designed to process liquids. Disclosure of the invention

[0003] Against this background, the approach presented here provides a microfluidic device, a method and a device for operating a microfluidic device, and finally, a corresponding computer program according to the main claims. The measures listed in the dependent claims enable advantageous refinements and improvements of the device specified in the independent claim.

[0004] The advantages achievable with the approach presented here are, in particular, that a microfluidic device is created that can enable reliable processing of a liquid.

[0005] A microfluidic device for processing a liquid is presented. The microfluidic device has a channel, a first branch channel, a first sealing element, a second branch channel, a second sealing element, and at least one resistance element. A first channel branch is connected to the first branch channel for fluidic connection of the channel. The first sealing element has a first valve and preferably a second valve, wherein the first sealing element is arranged between the first channel branch and the first branch channel. A second channel branch is connected to the second branch channel for fluidic connection of the channel. The second sealing element has a further valve, wherein the second sealing element is arranged between the second channel branch and the second branch channel.The resistance element is arranged on or in the channel and additionally or alternatively between the first channel branch and the second channel branch and additionally or alternatively between the first valve and the second valve.

[0006] The microfluidic device can be a lab-on-chip cartridge and / or referred to as a microfluidic analysis device and be designed to enable particularly reliable processing of a liquid, such as a sample liquid. The approach presented here can therefore also be understood as a microfluidic device for improved process control. The microfluidic device can be implemented as a polymeric multilayer system. By implementing the microfluidic device in the form of a polymeric multilayer system, particularly simple and standardized production of the device can be enabled using series production processes such as injection molding, stamping, or laser transmission welding.

[0007] The channel can be a microfluidic channel and form a high-pressure channel section between the first channel branch and the resistance element and a low-pressure channel section between the second channel branch and the resistance element. The resistance element can represent a barrier.

[0008] The high-pressure channel section can preferably be connected to a pump, for example a pump chamber, or a pressure reservoir in order to adjust a pressure in the high-pressure channel section. Preferably, no further resistance element or entity causing a pressure drop is located between the high-pressure channel section and the pump or the pressure reservoir. The high-pressure channel section can be part of a high-pressure channel network, which can have at least one microfluidic pump chamber or at least one further channel branch. Sealing of the microfluidic pump chamber or the at least one channel branch can be possible via sealing elements with a respectively increased fluidic resistance, in particular a respectively enlarged sealing surface.

[0009] A channel branch can be understood as a channel intersection, in particular an intersection where three channels meet or, in other words, where one channel splits into two channels, for example, a T-shaped intersection. In particular, the channel branch serves to create a fluidic connection between one channel and a branch channel.

[0010] The valves can be shaped similarly, in particular with regard to their sealing surface and / or their displacement volume. In particular, one or more of the valves are diaphragm valves. A sealing surface of a sealing element, in particular of a valve, can be understood in particular as a surface transverse to a predetermined fluid direction, which must be made inaccessible to a fluid, in particular by pressing a valve diaphragm against it, in order to prevent fluid flow through the sealing element or valve. If the sealing element has a plurality of valves, some of which can be connected in series and / or in parallel, the fluidic resistance, in particular the flow resistance against a fluid entering the valve, results from the interaction of the fluidic resistances of the plurality of valves depending on their connection to one another.In particular, the sealing surface of the sealing element is effectively created by the interaction of the sealing surfaces of the multiple valves, depending on their interconnection. The fluidic resistance of a sealing element or valve is understood to mean, in particular, a resistance to the flow of an incoming fluid through the sealing element or valve (flow resistance), particularly when the sealing element or valve is closed. A similar implementation of the microfluidic valves enables particularly simple and standardized production of the microfluidic device. Furthermore, the individual valves can each have comparable properties, for example, with regard to switching behavior, closing behavior, sticking behavior, and sealing behavior.Consequently, a particularly simple physical description and modeling as well as design of the microfluidic system may be possible, which may simplify and / or accelerate the development of such a device, as well as facilitate functional validation and / or functional testing.

[0011] The approach presented here can enable particularly reliable processing of a liquid, such as a sample liquid, using a microfluidic resistance element, for example, comprising a filter element or a channel taper, in particular a channel taper in cross-section of at least 50%, preferably at least 80%, or another obstacle structure in the channel. In particular, if the microfluidic resistance element has a particularly high microfluidic resistance and / or a liquid is used that has a particularly high viscosity or chemical affinity to a surface of the microfluidic device, reliable microfluidic processing of the liquid within the microfluidic device can be enabled.

[0012] In other words, microfluidic devices, which can also be referred to as microfluidic analysis systems, so-called lab-on-chips (LoCs for short), enable automated, reliable, fast, compact, and cost-effective processing of patient samples for medical diagnostics. By combining a variety of operations for the controlled manipulation of fluids, complex molecular diagnostic test sequences can be performed in a lab-on-chip cartridge, which can also be referred to as a microfluidic analysis device or apparatus. Lab-on-chip cartridges can, for example, be manufactured cost-effectively from polymers using serial production processes such as injection molding, stamping, or laser transmission welding. The processing of a lab-on-chip cartridge can take place in an associated analytical device.

[0013] When developing a microfluidic analysis device for a microfluidic analysis system, the question of a particularly advantageous design of the microfluidic network of the analysis device, in which the liquids are processed, arises. Fundamentally, the design of the microfluidic network depends on the chosen type of liquid transport within the microfluidic analysis device. Depending on the liquid transport principle, a distinction is made between different types of microfluidic analysis systems: One class, for example, is centrifugal microfluidic analysis systems. In these systems, fluid transport within the microfluidic analysis device is based on centrifugal, Coriolis, and Euler forces, which are generated by setting the microfluidic analysis device into a targeted rotational motion.

[0014] Another class is pressure-based microfluidic analysis systems. In these systems, fluid transport within the microfluidic analysis device occurs through the application of pressure, usually pneumatic. By locally applying positive or negative pressure, an elastic membrane, for example, as a component of the microfluidic analysis device, can be specifically deflected into recesses within the microfluidic analysis device, thereby sucking in or expelling fluid from the recesses. The elastic membrane simultaneously creates a separation between the microfluidic, fluid-carrying areas of the analysis device, on the one hand, and the pneumatic areas and the external environment, on the other.Consequently, contamination of the external environment with a sample liquid in the microfluidic device or, conversely, contamination of the sample liquid in the microfluidic device by interaction with the external environment can be prevented.

[0015] Depending on the size of a recess in a fluid-conducting region and the associated displacement volume upon deflection of the membrane into this region, for example, a microfluidic pump chamber with a larger displacement volume is provided for the primary generation of a flow in the device, or a microfluidic valve with a smaller displacement volume is provided for the primary control of the flow in the device. By combining at least three microfluidic pump chambers and / or valves, a directed flow can be generated in the microfluidic analysis device by successive actuation of the elements. For example, a pump chamber can be combined with two surrounding valves, i.e., an inlet valve and an outlet valve, to achieve directed fluid transport.In addition, for example, three similar elements with comparable displacement volumes can be combined to achieve peristaltic fluid transport through serial, successive actuation.

[0016] In general, such a microfluidic analysis device with pressure-based control has a plurality of active microfluidic elements, such as valves and pump chambers, which are interconnected in a suitable network of microfluidic channels. The pneumatic control of the active microfluidic elements is achieved via pneumatic microchannels within the microfluidic device, which can be subjected to positive or negative pressure via a pneumatic interface, advantageously designed as compactly as possible, between the microfluidic analysis device and the analysis device, which simultaneously functions as a processing unit. This induces actuation of the microfluidic elements by correspondingly deflecting the elastic membrane.

[0017] Advantageously, the actuation of the active microfluidic elements is carried out using an external analysis device, which can also be referred to as a process device, which has as few, in particular only two, pressure vessels as possible, in each of which a pneumatic pressure is present in a predetermined range, wherein the pressure can be provided, for example, by a controlled operation of pumps.However, the use of only two external pressure levels, specifically a high-pressure level and a low-pressure level, for actuating the active microfluidic elements of the device simultaneously presents the challenge of reliable process control within the device, especially if the pneumatic actuation pressure applied to a pump chamber to establish flow within the device is equal to the actuation pressure applied to the valves to control the flow within the device. Reliable microfluidic process control should also be possible in the event of increased microfluidic resistance along a pump path.

[0018] The approach presented here can create a microfluidic device with an advantageous design of the microfluidic network, which can enable particularly robust and reliable microfluidic process control, in particular in the case where a channel section has an increased microfluidic resistance and / or actuation of the pump chambers and valves occurs with the same pneumatic pressure level. In particular, improved microfluidic processing can be enabled for liquids with a high viscosity or chemical affinity to the surfaces of the microfluidic device, for example due to a similar polarity. To achieve this, undesired passage of liquid through sealing elements can be prevented by a particularly advantageous design or arrangement of the sealing elements.In this way, for example, the occurrence of microfluidic cross-contamination between different process steps—that is, the unwanted mixing of different liquid solutions used during a test procedure—can be prevented. Overall, this ensures particularly robust functionality with high reliability.

[0019] The approach presented here can be verified by optical inspection, particularly of cross-sections, and optionally using various microscopy techniques, such as light microscopy and / or fluorescence microscopy. The application presented here can be used, for example, for microfluidic lab-on-chip systems for medical diagnostics.

[0020] The first valve and the preferably second valve can be connected in series. This arrangement can represent a double-valve seal. The valves can seal the first branch channel from the first channel branch. The valves can increase fluid resistance, in particular a sealing surface, and can be manufactured using a standardized manufacturing process, thereby reducing costs.

[0021] The valves can be controlled via a common pneumatic channel with a single tap point and precisely one common pneumatic port of the microfluidic device. Such multiplexed control of pneumatically controlled active microfluidic elements can, on the one hand, reduce the number of pneumatic ports and thus the complexity of the pneumatic interface of the microfluidic device and / or, on the other hand, increase the achievable functionality of the device.

[0022] The first valve, the second valve, and additionally or alternatively the further valve can comprise an elastic polymer membrane. In other words, the valves can be realized using the elastic polymer membrane, which can be used to control the microfluidic flow within the microfluidic channel by applying pneumatic pressure. The use of an elastic polymer membrane, which can be deflected into fluid-conducting structures by applying pneumatic pressure, enables cost-effective and mass-produced microfluidic devices in the form of a polymer multilayer structure. In particular, the use of thermoplastic polymers can be advantageous, allowing particularly simple assembly of the individual plastic components using laser transmission welding.On the other hand, the use of the polymer membrane can achieve a fluid-tight separation between pneumatics and fluidics, thus preventing contamination of the sample liquid by the environment or, conversely, contamination of the environment by the sample liquid.

[0023] The resistance element can be designed as a filter element. The filter element can be used, for example, to extract components from a sample substance. The integration of a filter element can be particularly suitable for carrying out molecular diagnostic tests within the microfluidic device, for example, in conjunction with selective sample purification, in which components of a sample such as bacteria, viruses, cells, or molecular components thereof, such as DNA or RNA, can be extracted for analysis.

[0024] A fluidic resistance, in particular a sealing surface, of the first sealing element can be greater than a fluidic resistance, in particular a sealing surface, of the second sealing element, or the fluidic resistances, in particular the sealing surfaces, of the sealing elements can be identical. Preferably, the fluidic resistance, in particular the sealing surface, of the first sealing element is at least 50%, preferably at least 70%, and very preferably at least 100% greater than the fluidic resistance, in particular the sealing surface, of the second sealing element. Due to the increased fluidic resistances, in particular the increased sealing surface of the sealing elements that border the high-pressure channel section, particularly reliable microfluidic processing can be achieved in this area.Likewise, reliable microfluidic processing can be achieved in the low-pressure channel section by adequate sealing of the adjacent microfluidic structures, whereby overall - through the combination of sealing elements with an increased fluidic resistance, in particular an enlarged sealing surface, adjacent to the high-pressure region and sealing elements with a normal fluidic resistance, in particular a normal sealing surface, adjacent to the low-pressure region - in addition to the improved functionality of the device, also improved manufacturability and reduced complexity of the system can be enabled.

[0025] The microfluidic device can have a pumping chamber that can be fluidically connected to the first channel. In particular, the pumping chamber can be arranged adjacent to the resistance element and configured to generate a hydraulic pressure in the first channel or second channel. In other words, the high-pressure channel section can be adjacent to the microfluidic pumping chamber. The pumping chamber can be used to generate a hydraulic pressure in the high-pressure channel section. By implementing the microfluidic pumping chamber directly adjacent to the high-pressure channel section, a particularly simple establishment of the high-pressure level in the high-pressure channel section can be enabled. The pumping chamber can be actuated pneumatically via a pneumatic channel and a pneumatic port.Pneumatic actuation of the microfluidic pump chamber enables control of both the microfluidic pump chamber and microfluidic valves via a common pneumatic interface. If necessary, actuation of the microfluidic elements can occur via just one high-pressure level and one low-pressure level. The high-pressure level can be above the ambient pressure, which can be present at vent openings of the microfluidic device. The low-pressure level can be below the ambient pressure. Furthermore, the absolute values ​​of the relative pressures of the high-pressure level and the low-pressure level preferably differ from one another. For example, the relative high-pressure level is +1400 millibars relative to the ambient pressure, and the relative low-pressure level is -700 millibars relative to the ambient pressure.In this way, using the two pressure levels and different control sequences, pumping strategies optimized for each application can be used within the microfluidic device.

[0026] The microfluidic device may include at least one venting element for venting the microfluidic device. The venting element may have a pressure level that may correspond to the ambient pressure of the microfluidic device.

[0027] The microfluidic device can have a first pneumatic channel and a second pneumatic channel. The first pneumatic channel can be configured to control the first valve, and the second pneumatic channel can be configured to control the second valve. The pneumatic channels can be configured to couple the microfluidic device to a processing device via at least one pneumatic port. In other words, the two microfluidic valves can have two separate pneumatic channels for implementing the first sealing element, each of which can be configured with two separate pneumatic ports for external control. By implementing such a double-port seal, a particularly reliable seal can be achieved by sealing the first branch channel adjacent to the high-pressure channel section in a redundant manner.For example, even in the assumed fault case that a drop in the pneumatic pressure level occurs at one of the pneumatic control ports, sealing of the branch channel and / or the channel section via the further pneumatic port can still be ensured.

[0028] A processing device comprises a control unit, a first pump, a second pump, a first pressure reservoir, a second pressure reservoir, and at least one pneumatic port. The control unit is connected to the pumps via at least one signal line. The first pressure reservoir is pneumatically connected to the first pump, and the second pressure reservoir is pneumatically connected to the second pump. The pneumatic manifold, comprising a plurality of pneumatic ports, is pneumatically connected to the first pressure reservoir and the second pressure reservoir and is configured to pneumatically connect the individual pneumatic ports either to the first pressure reservoir or to the second pressure reservoir and further to couple the processing device to the microfluidic device.

[0029] A method for operating an embodiment of a microfluidic device mentioned herein comprises a step of controlling the first valve, the second valve and / or the further valve to operate the microfluidic device.

[0030] This method can be implemented, for example, in software or hardware or in a mixed form of software and hardware, for example in a control unit.

[0031] Furthermore, a method for particularly advantageously carrying out a test procedure in such a microfluidic device can be enabled.

[0032] A method for operating a further embodiment of a microfluidic device mentioned herein comprises a step of defining a pumping path and a step of establishing a pumping path by pneumatic actuation of sealing elements.

[0033] The method may include an additional step of pumping fluid along a predetermined pumping path.

[0034] The method may include a step of establishing a pneumatic interface between an external pneumatic processing device and a microfluidic device.

[0035] The sealing elements and, if applicable, the pumping chamber can be actuated via precisely one high-pressure level (overpressure level relative to the external pressure) and precisely one low-pressure level (underpressure level relative to the external pressure). This allows for a particularly simple design of the external process device, since only two pressure vessels are provided to provide the pressure levels.

[0036] The approach presented here further provides a control unit configured to perform, control, or implement the steps of a variant of a method presented here in corresponding devices. This embodiment of the invention in the form of a control unit also allows the problem underlying the invention to be solved quickly and efficiently.

[0037] For this purpose, the control unit can have at least one computing unit for processing signals or data, at least one memory unit for storing signals or data, at least one interface to a sensor or an actuator for reading sensor signals from the sensor or for outputting control signals to the actuator, and / or at least one communication interface for reading or outputting data embedded in a communication protocol. The computing unit can be, for example, a signal processor, a microcontroller, or the like, wherein the memory unit can be a flash memory 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 that can read in or output wired data can read this data, for example, electrically or optically from a corresponding data transmission line or output it to a corresponding data transmission line.

[0038] In this context, a control unit can be understood as an electrical device that processes sensor signals and outputs control and / or data signals depending on them. The control unit can have an interface that can be implemented in hardware and / or software. In a hardware implementation, the interfaces can, for example, be part of a so-called system ASIC, which contains a wide variety of functions of the control unit. However, it is also possible for the interfaces to be separate integrated circuits or to consist at least partially of discrete components. In a software implementation, the interfaces can be software modules that are present, for example, on a microcontroller alongside other software modules.

[0039] Also advantageous is a computer program product or computer program with program code that 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 to carry out, implement and / or control the steps of the method according to one of the embodiments described above, in particular when the program product or program is executed on a computer or a device.

[0040] Examples of the approach presented here are shown in the drawings and explained in more detail in the following description. It shows: Fig. 1 shows an embodiment of a microfluidic device; Fig. 2 shows an illustration of an embodiment of a microfluidic device; Fig. 3 a representation of an embodiment of a microfluidic device Fig. 4 shows an illustration of an embodiment of a microfluidic device; Fig. 5 shows an illustration of an embodiment of a microfluidic device; Fig. 6 is a flowchart of an embodiment of a method for operating a microfluidic device; Fig. 7 is a block diagram of an embodiment of a control device for operating a microfluidic device; and Fig. 8 a flow diagram of an embodiment of a method for operating a microfluidic device.

[0041] In the following description of advantageous embodiments of the present invention, the same or similar reference numerals are used for the elements shown in the various figures and having a similar effect, whereby a repeated description of these elements is omitted.

[0042] Fig. 1 shows an illustration of an embodiment of a microfluidic device 100. The microfluidic device 100 is configured to process a liquid.

[0043] For this purpose, the microfluidic device 100 has a channel 50, a first branch channel 555, a first sealing element 31, a second branch channel 555, a second sealing element 32a, and at least one resistance element 20. A first channel branch 550 is arranged between the channel 50 and the first branch channel 555, fluidically connecting the channel 50 and the first branch channel 555. The first sealing element 31 with a first valve 31a and a second valve 31b is arranged on the first branch channel 555. The valves 31a, 31b are connected in series merely by way of example.

[0044] A second channel branch 520 is arranged between the channel 50 and the second branch channel 525, which fluidically connects the channel 50 and the second branch channel 525. The second sealing element 32a with a further valve 32 is arranged on the second branch channel 525. The valves 31a, 31b, 32 are designed, for example, similarly, in particular as diaphragm valves, and / or have an elastic polymer membrane. The sealing elements 31, 32a each have a sealing surface, wherein a sealing surface of the second sealing element 32a is merely exemplary larger than a sealing surface of the first sealing element 31. Alternatively, the fluidic resistances, i.e., here the sealing surfaces of the sealing elements 31, 32a, are shaped identically.

[0045] The resistance element 20 is arranged on the channel 50 and is, for example, a filter element. A section of the channel 50 is formed, for example, between the resistance element 20 and the first channel branch 550 as a high-pressure channel section 55. Another section of the channel 50 is formed, merely by way of example, between the resistance element 20 and the second channel branch 520 as a low-pressure channel section 52.

[0046] In other words, the microfluidic device 100, which can also be referred to as a microfluidic analysis device, comprises a microfluidic network consisting of the microfluidic channel 50, on which at least the microfluidic resistance element 20 is arranged. The resistance element 20 is, for example, a filter element, wherein the resistance element 20 has a significant microfluidic resistance—for example, a resistance that leads to a pressure drop of, for example, at least 10 percent behind and before the filter element, so that when hydraulic pressure is applied in the system, the high-pressure channel section 55 is present upstream of the resistance element 20 and the low-pressure channel section 52 is present downstream of the resistance element 20.

[0047] Adjacent to the high-pressure channel section 55 is at least the first channel branch 550 leading to a first additional channel 555. Between the first channel branch 550 and the first branch channel 555, which can also be referred to as the first additional channel, a seal is created by at least the first sealing element 31, which can also be referred to as the first pneumatically actuated sealing element. Adjacent to the low-pressure channel section 52 is at least the second channel branch 520 leading to the second branch channel 525, which can also be referred to as the second additional channel 525.Between the second channel branch 520 and the second branch channel 525, a seal is created by at least the second sealing element 32a, which can also be referred to as a second pneumatically actuated sealing element, wherein the sealing surface of the first sealing element 31 is larger than or at least equal to the sealing surface of the second sealing element 32a. This has the particular advantage that, due to the increased fluidic resistance of the sealing element 31, which borders the high-pressure channel section 55, particularly reliable microfluidic processing can be achieved in this region.Likewise, in the low-pressure channel section 52, reliable microfluidic processing can be achieved by adequate sealing of the adjacent microfluidic structures, whereby overall - through the combination of a sealing element 31 with an enlarged sealing surface adjacent to the high-pressure channel section 55, which can also be referred to as the high-pressure region, and a sealing element 32a with a conventional sealing surface adjacent to the low-pressure channel section 52, which can also be referred to as the low-pressure region - in addition to the improved functionality of the microfluidic device 100, improved manufacturability and reduced complexity of the system are also provided.

[0048] The first sealing element 31 is implemented by at least the two microfluidic valves 31a, 31b, and the second sealing element 32a is implemented by at least the further microfluidic valve 32. This advantageous embodiment of the first sealing element 31 can also be referred to as a double-valve seal, since two valves 31a, 31b are used to seal the first branch channel 555 from the first channel branch 550, which can also be referred to as a branching point, at the high-pressure channel section 55.

[0049] Due to the increased sealing surface and thus the increased fluidic resistance, a particularly reliable sealing of the first branch channel 555 is possible, and a standardized production of the valves 31a, 31b, 32 is also possible. This, in turn, enables a particularly simple and cost-effective production of the device 100, for example, using an arrangement of polymer components that can be joined together by laser transmission welding.

[0050] In other words, Fig. 1 shows a schematic representation of an embodiment of the microfluidic device 100 with a microfluidic network comprising at least the first microfluidic channel 50, on which at least the microfluidic resistance element 20—such as a filter element—is arranged, wherein the microfluidic resistance element 20 has a significant microfluidic resistance—for example, a resistance that leads to a pressure drop of, for example, at least 10 percent between the channel region behind and in front of the filter element, so that a high-pressure channel section 55 is present in front of the resistance element 20 and a low-pressure channel section 52 is present behind the resistance element 20.wherein at least the first channel branch 550 to the first branch channel 555 is arranged adjacent to the high-pressure channel section 55, and between the first channel branch 550 and the first branch channel 555, the seal is produced by at least the first sealing element 31. At least one second channel branch 520 to the second branch channel 525 is arranged adjacent to the low-pressure channel section 52, and between the second channel branch 520 and the second branch channel 525, the seal is produced by at least the second sealing element 32a, wherein the sealing surface of the first sealing element 31 is larger than or at least equal to the sealing surface of the second sealing element 32a. The network of the microfluidic device 100, which can also be referred to as a microfluidic analysis device, is composed of the microfluidic channels 50, 52, 55, 525, 555, which are shown schematically as solid lines,which connect the various microfluidic elements, in particular the resistance element 20 and the sealing elements 31, 32a, with each other, wherein the network additionally has two nodes or channel branches 520, 550. Similar microfluidic elements are each represented schematically by the same reference numerals. For example, a sample to be filtered can be conveyed via the first branch channel 555 to the resistance element 20, in particular applied to a filter element as the resistance element 20. Subsequently, a liquid, for example a washing or elution buffer, can be conveyed directly to the resistance element 20 via the channel branch 550, without using the branch channel 555, in particular applied to a filter element as the resistance element 20.in particular by utilizing a pressure that is higher than that of the first branch channel 555. Alternatively, this fluid can also be guided to the filter element via the branch channel 555, whereby the increased pressure in the high-pressure channel section 55 is also utilized.

[0051] In the exemplary embodiment, an increased fluidic resistance is advantageously achieved via an enlarged sealing surface of the first sealing element 31 compared to the second sealing element 32a, by a configuration of the first sealing element 31, which can also be referred to as a sealing element, by the two microfluidic valves 31a, 31b and a configuration of the second sealing element 32a, which can also be referred to as a sealing element, by the further microfluidic valve 32, wherein the microfluidic valves 31a, 31b, 32 of the first and second sealing elements 31, 32a are all designed identically. This advantageously allows, for example, a standardized and thus particularly simple, reliable, and cost-effective production of the three microfluidic valves 31a, 31b, 32 and ultimately of the microfluidic device 100.The microfluidic valves 31a, 31b, 32 are designed in particular as pneumatic valves, which can each be actuated via pneumatic control channels.

[0052] Fig. 2 shows an illustration of an embodiment of a microfluidic device 100. The microfluidic device 100 is similar or corresponds to the microfluidic device of Fig. 1, except that the microfluidic device 100 is connected to a processing device 200.

[0053] For this purpose, the microfluidic device 100 has, for example, a first pneumatic channel 71a, a second pneumatic channel 71b, a further pneumatic channel 72, and pneumatic ports 731a, 731b, 732. The first pneumatic channel 71a is arranged, merely by way of example, between the first valve 31a and a first port 731a. The second pneumatic channel 71b is arranged, for example, between the second valve 31b and a second port 731b. The further pneumatic channel 72 is arranged, for example, between the further valve 32 and a further port 732.

[0054] The ports 731a, 731b, 732 are designed, for example, to enable a connection between the microfluidic device 100 and the processing device 200.

[0055] The process device 200 has a control unit 210, a first pump 271, a second pump 272, a first pressure reservoir 291, a second pressure reservoir 292, and, for example, a plurality of pneumatic ports 231a, 231b, 232. The control unit 210 is connected to the pumps 271, 272 via at least one signal line each. The first pump 271 is connected, for example, to the control unit 210 via a signal line and is pneumatically connected to the first pressure reservoir 291. The second pump 272 is connected, for example, to the control unit 210 via a signal line and is pneumatically connected to the second pressure reservoir 292.

[0056] According to one embodiment, the process device 200 has a plurality of multi-way valves 251a, 251b, 252. The multi-way valves 251a, 251b, 252 are connected, for example, via channels to the pressure reservoirs 291, 292 and the pneumatic ports 231a, 231b, 232. More specifically, the multi-way valve 251a is connected, for example, to a first pneumatic port 231a and, via a tapping point on a pneumatic line, to the first pressure reservoir 291 and, via another pneumatic line, to the second pressure reservoir 292. The multi-way valve 251b is connected, for example, to a second pneumatic port 231b and, via two tapping points, to the first pressure reservoir 291 and to the second pressure reservoir 292. The multi-way valve 252 is connected, merely by way of example, between a third port 232 and via a tapping point to the second pressure reservoir 292 and via a further pneumatic line to the first pressure reservoir 291.The multi-way valves 231a, 231b, 232 can also be controlled via the control unit 210.

[0057] According to one embodiment, the pneumatic port 231a of the processing device 200 is coupleable to the pneumatic port 731a of the microfluidic device 100. For example, the pneumatic port 231b of the processing device 200 is coupleable to the pneumatic port 731b of the microfluidic device 100, and the pneumatic port 232 of the processing device 200 is coupleable to the pneumatic port 732 of the microfluidic device 100.

[0058] In other words, the microfluidic device 100 is designed, for example, such that the two microfluidic valves 31a, 31b for realizing the first sealing element 31 have two separate pneumatic channels 71a, 71b, which are each designed with two separate pneumatic ports 731a, 731b for external control of the microfluidic device 100 with the processing device 200, which can also be referred to as external pneumatic processing device 200.

[0059] In other words, the process device 200 comprises the control unit 210, which can also be a regulating unit, as well as two pumps 271, 272, which, as outlined, are pneumatically connected to two pressure reservoirs 291, 292, and multi-way valves 251a, 251b, 252, which enable the application of pneumatic pressure to the ports 231a, 231b, 232, which can also be referred to as pneumatic ports. Via a pneumatic interface, the ports 231a, 231b, 232 of the process device 200 can be connected in a defined manner to the ports 731a, 731b, 732, which can also be referred to as pneumatic ports, of the microfluidic device 100. The pressure reservoirs 291, 292 have, in particular, different pressure levels from one another, which are greater or smaller than the ambient pressure under which the device is operated.Consequently, the pressure reservoirs 291, 292 have an overpressure or a negative pressure relative to the ambient pressure. The exemplary embodiment described here offers the advantage of enabling a simple and cost-effective implementation of the external pneumatic processing device 200, with only two pressure levels being required to control the microfluidic device 100. Fig. 3 shows an illustration of an embodiment of a microfluidic device 100. The microfluidic device 100 is similar or corresponds to the microfluidic device of Fig. 2, except that one port is omitted. The process device 200 is similar to the process device of Fig. 2, except that one port and one valve are omitted.

[0060] The valves 71a, 71b of the microfluidic device 100 are connected jointly to the pneumatic port 731 via a tapping point 710, whereby a port of the process device 200 and a port of the microfluidic device 100 as well as a valve of the process device 200 can be omitted.

[0061] In other words, Fig. 3 shows a schematic representation of an embodiment of the microfluidic device 100. The two microfluidic valves 31a, 31b are connected to a common pneumatic port 731 to implement the first sealing element 31, wherein a common control is possible via the pneumatic channels 71a, 71b with the tapping point, which can also be referred to as the branching point 710. This so-called multiplexing advantageously allows, on the one hand, an increased fluidic resistance, in particular an enlarged sealing surface of the first sealing element 31, to be produced, and, on the other hand, a pneumatic control of the first sealing element 31 takes place via only the one pneumatic port 731, which enables a particularly simple and cost-effective implementation of the microfluidic device 100 and the processing device 200.

[0062] The process device 200 comprises the control unit 210 or regulating unit 210 as well as the two pumps 271, 272, each of which is connected to one of the pressure reservoirs 291, 292, as well as two valves 251a, 252, which can also be referred to as multi-way valves, which enable pressurization of the pneumatic ports 231, 232.

[0063] Fig. 4 shows an illustration of an embodiment of a microfluidic device 100. The microfluidic device 100 is similar or corresponds to the microfluidic device of Fig. 1, except that the microfluidic device 100 has a pumping chamber 41, a third channel branch 551 and a third branch channel 556 and / or a fourth branch channel 557.

[0064] The pump chamber 41 is arranged, for example, adjacent to the resistance element 20 in the channel 50. More precisely, the pump chamber 41 is arranged merely by way of example between the first channel branch 550 and the further channel branch 551. Regardless of the presence of the third branch channel 556, however, there is preferably no further entity that could cause a substantial pressure drop in the channel 50, in particular no further resistance element, between the pump chamber 41 and the resistance element 20. This allows the full pump power 41 to act on the resistance element 20, in particular a filter. The third channel branch 551 is designed to fluidically connect the channel 50 to the third branch channel 556 and / or the fourth branch channel 557.

[0065] According to one embodiment, a fourth valve 33 is arranged between the pump chamber 41 and the further channel branch 551. A fifth valve 34 is arranged, for example, on the third branch channel 556, and a sixth valve 35 is arranged, for example, on the fourth branch channel 557.

[0066] In other words, Fig. 4 shows an embodiment of the microfluidic device 100. The high-pressure channel section 55 adjoins the microfluidic pump chamber 41, which can be used to generate a hydraulic pressure in the high-pressure channel section 55. Furthermore, the high-pressure channel section 55 extends adjacent to both sides of the pump chamber 41, wherein, starting from the high-pressure channel section 55 toward the channels 555, 556, 557 via the channel branches 550, 551, which can also be referred to as branching points, at least two of the total of five valves 31a, 31b, 33, 34, 35 are always present along each path, which allow a seal with an increased fluidic resistance, in particular an enlarged sealing surface.

[0067] Starting from the high-pressure channel region 55 towards the first branch channel 555, these are the microfluidic valves 31a and 31b, towards the third branch channel 556 these are the microfluidic valves 33 and 34, and towards the fourth branch channel 557 these are the microfluidic valves 33 and 35.

[0068] Fig. 5 shows an illustration of an embodiment of a microfluidic device 100. The microfluidic device 100 is similar to or corresponds to the microfluidic device from one of the figures described above.

[0069] According to one embodiment, the resistance element 20 is arranged in the channel 50 between the first valve 31a and the second valve 31b. More specifically, the resistance element 20 is arranged adjacent to the low-pressure channel section 52 of the channel 50.

[0070] The first valve 31a is arranged between the resistance element 20 and the first channel branch 550. The first channel branch 550 fluidically connects the channel 50 and the first branch channel 5505. The further valve 32 and the fourth valve 33, for example, are arranged in the first branch channel 5505.

[0071] Adjacent to the first channel branch 550, for example, the fifth valve 34 and the sixth valve 35 are arranged in the channel 50, more precisely in the high-pressure channel section 55.

[0072] According to one embodiment, a seventh valve 41 is arranged in the high-pressure channel section 55, wherein the third channel branch 551 is arranged between the sixth valve 35 and the seventh valve 41.

[0073] A fourth channel branch 5551 and a fifth channel branch 5556 are arranged, for example, in the high-pressure channel section 55. The fifth channel branch 5556 connects the channel 50 to a fifth branch channel 5565. Two valves 44a, 44b are arranged in the fifth branch channel 5565 purely by way of example.

[0074] The channel branches 5551, 5556 connect, for example, the channel 50 to a chamber 5555 with a venting element 5559. The chamber 5555 is shown, for example, in an open state, with a valve 42 arranged between the fourth channel branch 5551 and the chamber 5555 and with a valve 43 arranged between the fifth channel branch 5556 and the chamber 5555.

[0075] The pumping chamber 401 is arranged, for example, in the high-pressure channel section 55 of the channel 50. More precisely, the pumping chamber 401 is arranged between the third channel branch 551 and a sixth channel branch 552. The sixth channel branch 552, for example, fluidically connects the channel 50 to a second branch channel 5525. Two valves 37a, 37b are arranged in the second branch channel 5525.

[0076] For example, a valve 36 is arranged adjacent to the sixth channel branch 552. More specifically, the valve 36 is arranged between the sixth channel branch 552 and a seventh channel branch 553. The seventh channel branch 553, for example, fluidically connects the channel 50 to a third branch channel 5535, wherein a valve 40 is arranged in the third branch channel 5535.

[0077] The seventh channel branch 553 additionally or alternatively connects, for example, the channel 50 via an eighth channel branch 554 to a further chamber 5545 with a further venting element 5549. For example, a valve 38 is arranged between the chamber 5545 and the eighth channel branch 554, wherein a valve 39 is arranged parallel to the valve 38 between the chamber 5545 and the eighth channel branch 554.

[0078] According to one embodiment, the microfluidic device 100 has a pneumatic interface 700 with a plurality of pneumatic ports 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745. Ports 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745 are configured, for example, to control valves 31a, 31b, 32, 33, 34, 35, 36, 37a, 37b, 38, 39, 40, 41, 42, 43, 44a, 44b and / or pump chamber 401. Port 737 is configured, for example, to control pump chamber 401. According to one embodiment, one port can control multiple valves, such as port 738, which controls valves 31a, 31b.

[0079] In other words, Fig. 5 shows the microfluidic device 100 with the high-pressure channel section 55, the microfluidic resistance element 20, which is designed as a filter element, for example, the low-pressure channel section 52, channel branches 550, 551, 552, 553, 554, 5551, 5556, valves 31a, 331b, 32, 33, 34, 35, 36, 37a, 37b, 38, 39, 40, 41, 42, 43, 44a, 44b, which can also be referred to as microfluidic sealing valves, the microfluidic pump chamber 40, the microfluidic channels 5505, 5525, 5535, 5565 and chambers 5545, 5555 with venting elements 5549, 5559 and the pneumatic interface 700 with pneumatic ports 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745. The device 100 is characterized in that the microfluidic channels 5505, 5525, 5535, 5565 and chambers 5545, 5555 with venting elements 5549, 5559 are always sealed by at least two microfluidic sealing valves each.The venting elements 5549, 5559 enable venting of the microfluidic network and have a pressure level corresponding to the ambient pressure of the microfluidic device 100.

[0080] According to one embodiment, the microfluidic channel 5505 is sealed from the channel branch 550 of the high-pressure channel section 55 of the channel 50 by the valves 32 and 33.

[0081] According to a further embodiment, the microfluidic channel 5525 is sealed from the channel branch 552 of the high-pressure channel section 55 by the valves 37a, 37b. The microfluidic channel 5535 is separated from the channel branches 552, 553 of the high-pressure channel section 55, for example, by the valves 36, 40.

[0082] According to a further embodiment, the microfluidic channel 5565 is sealed from the channel branches 551, 5556 at the high-pressure channel section 55 by the valves 44a, 44b.

[0083] According to a further embodiment, the chamber 5545 with the venting element 5549 is sealed from the channel branches 552, 553, 554 at the high-pressure channel section 55 by the valves 36, 38, or the valve 39.

[0084] According to a further embodiment, the chamber 5555 is sealed with the venting element 5559 from the channel branches 551, 5551, 5556 at the high-pressure channel section 55 via the valves 41, 42 and the valve 43, respectively.

[0085] The following are exemplary dimensions and specifications of an implementation of the microfluidic device 100 as described in the above-mentioned embodiment.

[0086] The overall lateral dimensions of the microfluidic device 100 are, for example, 50 x 25 square millimeters to 300 x 200 square millimeters, preferably 75 x 25 square millimeters to 200 x 100 square millimeters, for example 160 x 78 square millimeters.

[0087] The cross-sectional dimensions of the fluidic and pneumatic microchannels are, for example, 100 x 100 square micrometers to 3 x 3 square millimeters, preferably 300 x 300 square micrometers to 1 x 1 square millimeter, for example 400 x 600 square micrometers for fluidic microchannels and 400 x 500 square micrometers for pneumatic microchannels.

[0088] The effective displacement volume of a microfluidic pump chamber 41 is, for example, 1 microliter to 50 microliters, preferably 5 microliters to 30 microliters, for example 25 microliters.

[0089] The effective displacement volume of a microfluidic valve 31a is, for example, 80 nanoliters to 1 microliter, preferably 100 nanoliters to 300 nanoliters.

[0090] The sealing surface of a microfluidic valve 31a is, for example, 0.1 square millimeters to 10 square millimeters, preferably 0.5 square millimeters to 5 square millimeters, for example, 2 square millimeters. For example, the valves are diaphragm valves.

[0091] The volume of the microfluidic chamber with filter element 20 is, for example, 3 microliters to 20 microliters, preferably 5 microliters to 10 microliters. The filter element 20 is, for example, a silica filter.

[0092] The pressure difference, i.e. overpressure or underpressure, relative to the ambient pressure, which is used to generate the microfluidic flow by squeezing or sucking in by means of a pump chamber 41 is, for example, 100 millibar to 2000 millibar, preferably 400 millibar to 1500 millibar, for example 700 millibar underpressure and 1400 millibar overpressure.

[0093] The materials for the realization of the microfluidic device 100 are, for example, primarily polymers such as polycarbonate (PC for short), polystyrene (PS for short), styrene-acrylonitrile copolymer (SAN for short), polypropylene (PP for short), polyethylene (PE for short), cycloolefin copolymer (COP for short), COC for short, polymethyl methacrylate (PMMA for short), polydimethylsiloxane (PDMS for short), or thermoplastic elastomers (TPE for short), such as polyurethane (TPU for short) or styrene block copolymer (TPS for short); for example, manufactured by series production processes such as injection molding, thermoforming, punching, or laser transmission welding.

[0094] The sample substance that can be processed within the microfluidic analysis device 100 is, for example, a liquid, for example, an aqueous solution, for example, obtained from a biological substance, for example of human origin, such as a body fluid, a swab, a secretion, sputum, a tissue sample, or a device with attached sample material. The sample fluid contains, for example, species of medical, clinical, diagnostic, or therapeutic relevance, such as bacteria, viruses, cells, circulating tumor cells, cell-free DNA, proteins, or other biomarkers, or in particular, components of the aforementioned objects.For example, the sample liquid is a master mix or components thereof, for example for carrying out at least one amplification reaction in the receiving element, for example for DNA detection at the molecular level such as an isothermal amplification reaction or a polymerase chain reaction.

[0095] Liquids for processing within the microfluidic analysis device 100 are, for example, aqueous solutions, for example buffer solutions, for example with components of a sample substance; mineral oils, silicone oils, fluorinated hydrocarbons.

[0096] Fig. Figure 6 shows a flowchart of an embodiment of a method 600 for operating a microfluidic device. The microfluidic device is, for example, a microfluidic device described in the preceding figures.

[0097] The method 600 comprises a step 605 of controlling the first valve, the second valve, and / or the further valve to operate the microfluidic device.

[0098] Fig. Figure 7 shows a block diagram of an embodiment of a control device 700 for operating a microfluidic device. The control device 700 is designed to implement the method of Fig. 6 or a similar method. For this purpose, the control device 700 has a unit 705 for controlling the first valve, the second valve, and / or the further valve to operate the microfluidic device.

[0099] Fig. Figure 8 shows a flowchart of an embodiment of a method 800 for operating a microfluidic device. The microfluidic device is, for example, a microfluidic device described in the preceding figures.

[0100] The method 800 comprises a step 805 of defining a pumping path, a step 810 of establishing a pneumatic interface between an external pneumatic processing unit and a microfluidic device, a step 815 of establishing a pumping path by pneumatically actuating sealing elements of the microfluidic device, and a step 820 of pumping liquid along the pumping path defined in step 805.

[0101] In further embodiments of the method 800, individual steps can be omitted or swapped in order with other steps.

[0102] The features described in the exemplary embodiments can each be implemented individually and / or in combination with one another. If an exemplary embodiment includes an "and / or" connection between a first feature and a second feature, this should be interpreted as meaning that, according to one embodiment, the exemplary embodiment includes both the first feature and the second feature, and according to another embodiment, either only the first feature or only the second feature.

Claims

[1] Microfluidic device (100) for processing a liquid, the microfluidic device (100) having the following features: a channel (50); a first branch channel (555; 5505), wherein a first channel branch (550) is connected to the first branch channel (555) for fluidically connecting the channel (50); a first sealing element (31) with a first valve (31a) and preferably a second valve (31b), wherein the first sealing element (31) is arranged between the first channel branch (550) and the first branch channel (555; 5505); a second branch channel (525; 5525), wherein a second channel branch (520; 552) is connected to the second branch channel (525; 5525) for fluidically connecting the channel (50); a second sealing element (32a) with a further valve (32), wherein the second sealing element (32a) is arranged between the second channel branch (520) and the second branch channel (525) or between the first channel branch (550) and the first branch channel (5505); and at least one resistance element (20) arranged on or in the channel (50) and between the first channel branch (550) and the second channel branch (520) and between the first sealing element (31) and the second sealing element (32a). [2] The microfluidic device (100) according to claim 1, wherein the first valve (31a) and the second valve (31b) are connected in series. [3] Microfluidic device (100) according to one of the preceding claims, wherein the first valve (31a), the second valve (31b) and / or the further valve (32) comprise an elastic polymer membrane. [4] Microfluidic device (100) according to one of the preceding claims, wherein the resistance element (20) is designed as a filter element. [5] Microfluidic device (100) according to one of the preceding claims, wherein a fluidic resistance, in particular a sealing surface, of the first sealing element (31) is greater than a fluidic resistance, in particular a sealing surface of the second sealing element (32a). [6] Microfluidic device (100) according to one of the preceding claims, comprising a pumping chamber (41) which is fluidically connected to the channel (50), optionally arranged directly adjacent to the resistance element (20) and is designed to generate a hydraulic pressure in the channel (50). [7] Microfluidic device (100) according to one of the preceding claims, comprising at least one venting element (5549) for venting the microfluidic device (100). [8] Microfluidic device (100) according to one of the preceding claims, comprising a first pneumatic channel (71a) and a second pneumatic channel (71b), wherein the first pneumatic channel (71a) is designed to control the first valve (31a) and the second pneumatic channel (71b) is designed to control the second valve (31b), wherein the pneumatic channels (71a, 71b) are designed and have at least one branching point (710) in order to couple the microfluidic device (100) to a processing device (200) via at least one pneumatic port (731). [9] Microfluidic device (100) according to one of the preceding claims, wherein the pneumatic channels (71a, 71b) are designed to couple the microfluidic device (100) to a processing device (200) via at least one pneumatic port (731a, 737b) in each case. [10] Microfluidic device (100) according to one of the preceding claims, wherein the fluidic resistances, in particular the sealing surfaces of the valves (31a, 31b, 32) are at least approximately equal within a predetermined tolerance range. [11] Process device (200) having the following features: a control unit (210); a first pump (271) and a second pump (272), wherein the control unit (210) is connected to the pumps (271, 272) via at least one signal line each; a first pressure reservoir (291) and a second pressure reservoir (292), wherein the first pressure reservoir (291) is arranged adjacent to the first pump (271), wherein the second pressure reservoir (292) is arranged adjacent to the second pump (272); and at least one pneumatic port (231a, 232b) which is pneumatically connected via a multi-way valve (251a, 252b) either to the first pressure reservoir (291) or to the second pressure reservoir (292) and is designed to couple the processing device (200) to the microfluidic device (100) according to one of claims 1 to 10. [12] A method (600) for operating a microfluidic device (100) according to any one of claims 1 to 10, wherein the method (600) comprises the following step: Controlling (605) the first valve (31a), the second valve (31b), and / or the further valve (32) to operate the microfluidic device (100). [13] Control device (700) which is configured to carry out and / or control the step (605) of the method (600) according to claim 12 in a corresponding unit (705). [14] Computer program configured to execute and / or control the step (605) of the method (600) according to claim 12. [15] A machine-readable storage medium on which the computer program according to claim 14 is stored.

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