Microfluidic device and method for operating a microfluidic device

Abstract

The invention relates to a microfluidic device (100) having a supply channel (110) for conducting a liquid (112), wherein the supply channel (110) opens into a channel junction (117). Furthermore, the device (100) comprises a first output channel (115) for further conducting the liquid (112), wherein the output channel is fluidically connected to the supply channel (110) via the channel junction (117), a valve preliminary channel (105) for further conducting the liquid (112), wherein the output channel is fluidically connected to the supply channel (110) via the channel junction (117), and a valve (125) arranged between the valve preliminary channel (105) and a second output channel (120). The valve preliminary channel (105) comprises a gas volume (130) for shielding the valve (125) with respect to the liquid (112) in a state of readiness of the device (100).

Description

Technical Field

[0001] The present invention relates to a microfluidic device of the type described in the independent claims and a method for operating the microfluidic device. Background Technology

[0002] Microfluidic analysis systems, also known as Lab-on-Chip (LoCs), allow for the automated, reliable, rapid, compact, and cost-effective processing of patient samples for medical diagnostics. Through a combination of controlled manipulations of the fluid, complex molecular diagnostic testing procedures can be implemented on the LoC shell. Summary of the Invention

[0003] Against this backdrop, a microfluidic device and a method for operating the microfluidic device according to the independent claim are proposed using the solutions described herein. Advantageous extensions and improvements to the device described in the independent claim can be achieved through the measures enumerated in the dependent claims.

[0004] The microfluidic device described herein is advantageously and appropriately constructed to prevent leakage through the seals of microfluidic valves. Furthermore, tolerances arising from manufacturing techniques or during the intended use of the device are permissible, without critically affecting the microfluidic functionality of the device. Particularly advantageously, sample material dissolved in a liquid can be microfluidically transported within the microfluidic device, where the formation of a liquid film in the sealing area of ​​the microfluidic valve can be prevented. Therefore, the device described herein can be used particularly advantageously to achieve sequential processes, i.e., microfluidic processes (in which different liquid solutions are pumped through areas of the microfluidic network), in a microfluidic system without undesirable mixing of different liquid solutions or loss of liquid solution volume typically associated with predetermined process steps due to leakage through the seals on the microfluidic valves.

[0005] A microfluidic device is described, comprising a supply channel for guiding liquid, wherein the supply channel leads into a channel engagement portion. Furthermore, the device includes: a first output channel for further guiding liquid, wherein the first output channel is fluidly connected to the supply channel via the channel engagement portion; a valve pre-channel for further guiding liquid, wherein the valve pre-channel is fluidly connected to the supply channel via the channel engagement portion; and a valve disposed between the valve pre-channel and the second output channel. The valve pre-channel, in a ready-to-operate state of the device, includes a gas volume for shielding the valve relative to the liquid. Preferably, the microfluidic device thus includes liquid, particularly capable of being situated in the valve pre-channel, wherein a gas volume exists between the liquid and the valve, particularly when the microfluidic device is used as intended. Therefore, a "ready-to-operate state" can preferably mean that at least a portion of the liquid is situated in the supply channel and / or the channel engagement portion and / or the valve pre-channel, and a gas volume is situated in the valve pre-channel. The gas volume can be a mixture of gases, such as air, or a single gas, such as nitrogen.

[0006] The valve pre-channel preferably has a predetermined maximum width, particularly the maximum lateral extension of the valve pre-channel's cross-section, based on the capillary length and / or surface tension of the liquid used. This advantageously stabilizes the geometry of the phase interface between the gas volume and the liquid, at least in the region adjacent to the channel engagement portion of the valve pre-channel, due to the surface tension. Here, the maximum width is preferably less than or equal to 1.5 times the capillary length. More preferably, the maximum width is less than the capillary length of the liquid.

[0007] The microfluidic device can be, for example, a microfluidic analysis cartridge for analyzing, for example, patient samples. As a supplement or alternative, the microfluidic device can be used for other microfluidic operations and applications, such as extracting components from sample material or culturing cells in a microfluidic system. For this purpose, the device can have multiple different microfluidic channels, valves, and chambers, which can be configured, for example, to guide liquids or to perform different reactions. The channel junctions can be, in particular, connections between multiple channels, allowing fluid to transfer from one of these channels to another. Preferably, the channel junctions connect three channels; in other designs, four or more channels are connected. The channel junctions can be intersections of multiple channels, such as a T-junction of three channels. In particular designs, the channel junctions can also have one or more additional valves for temporarily blocking the fluid. The liquid can, for example, contain sample material or sample substance that can be processed inside the microfluidic device. The sample material can be, for example, an aqueous solution, extracted from biological material of human origin, such as bodily fluids, smears, secretions, saliva, or tissue samples, or from a device with attached sample material. The sample liquid can be, for example, a species with medical, clinical, diagnostic, or therapeutic relevance, such as bacteria, viruses, cells, circulating tumor cells, cell-free DNA, proteins, or other biomarkers, or components thereof, particularly from the aforementioned objects. For example, the sample liquid can be a so-called mastermix or a component thereof, used, for example, to perform at least one amplification reaction, such as for DNA detection at the molecular level, like isothermal amplification or polymerase chain reaction.

[0008] To process sample materials, for example, the liquid used in the device can be guided through the supply channel with the valve closed. Here, especially when using diaphragm-based valves, it is important to prevent liquid from advancing into the valve, in order to prevent, for example, leakage of the seal in the valve area or, also, to prevent, for example, wetting of the valve by means of capillary forces. Accordingly, it is advantageous that a valve pre-channel is arranged between the supply channel and the valve in the device described herein. The valve pre-channel can also be referred to as a volumetric capillary valve pre-channel (KKVV channel) or, in English, a capacitive capillary valve pre-channel (CCVP channel). This relates to a functional element in the structure of the microfluidic system that can be used to improve liquid guidance in the microfluidic system and, in particular, to prevent possible leakage of the valve seal. The device is based in particular on the understanding that, at the valve (where the diaphragm is not in contact with the liquid), there will be no leakage of the valve by capillary forces, and short-term pressure fluctuations in the system are compensated by the capacity effect of the gas volume enclosed in the valve pre-channel before the valve, thereby preventing leakage of the valve downstream of the gas volume. Here, in addition to the capacity effect of the gas volume present in the valve pre-passage, the particularly advantageous functionality of the device described herein also arises from the capillary stability of the geometry of the phase interface present in the valve pre-passage, which results in the liquid that is squeezed into the valve pre-passage for a short time by pressure fluctuations being completely discharged from the valve pre-passage by the counterpressure formed in the enclosed gas volume.

[0009] According to one embodiment, the valve can be configured to separate a valve pre-channel from a second output channel. For example, if the liquid is to be directed from the supply channel to the first output channel for processing, the valve can be closed, thereby separating the second output channel from the valve pre-channel. In this advantageous manner, not only the valve but also the valve pre-channel can function as a separating element of the microfluidic functional unit. In this respect, the arrangement of microfluidic elements can be understood as a functional unit that, as a whole, provides at least one, and usually multiple, functionalities for implementing a microfluidic process. For example, the functional units can be used sequentially and continuously during the microfluidic process. It is desirable that no liquid delivery occurs in the functional unit before it is used as planned during the microfluidic process. Otherwise, this could adversely affect the functionality of the functional unit. In this respect, the valve pre-channel, together with the valve following it, thus serves as an inlet channel or gate for the controlled exchange of liquid with the microfluidic functional unit. This functionality enables reliable microfluidic insulation of each region of the microfluidic network of the device until its use, and prevents unwanted microfluidic crosstalk between different process steps in the microfluidic flow.

[0010] According to another embodiment, the valve pre-channel can be arranged substantially perpendicular to the supply channel, and as a supplement or alternative, substantially perpendicular to the first output channel. For example, the valve pre-channel, together with the valve following it, can be connected in a near-T-shape to other channels of the microfluidic network, such as the supply channel and the first output channel. Because the valve pre-channel is T-shaped to the channel of the microfluidic network, on the one hand, interface pinning can be advantageously achieved before the liquid is forced into the valve pre-channel. On the other hand, because the valve pre-channel, together with the valve following it, is connected almost perpendicularly to the liquid supply channel, inertial forces applied to the valve by the liquid can be prevented. In other words, necessary changes in direction or diversions of the liquid flow can be achieved, for example, by suitable channel guidance, in which the walls of the channel are subjected to inertial forces or pulse transmissions, which can be transmitted by the liquid when the liquid flow is diverted.

[0011] According to another embodiment, the valve pre-channel can be hydrophobically configured, and the supply channel and, as a supplement or alternative, the first output channel can be hydrophilically configured. For example, not only the supply channel but also the first output channel can be hydrophilically configured. Advantageously, this facilitates the guidance of liquid in these channels while preventing liquid from being forced into the hydrophobically configured valve pre-channel.

[0012] According to another embodiment, the device can be configured as a pressure-based system. For example, the pressure-based system can achieve controlled microfluidic liquid transport within the device by applying at least two pressure levels. Here, the device can, for example, be based on the use of a flexible diaphragm, which can be integrated into the device and used to establish liquid transport within a barrel. The latter can be achieved, for example, by a controlled, pressure-based, i.e., pneumatically controlled offset of the diaphragm towards a defined opening in the device, thereby inducing targeted extrusion of the liquid. Integrating a flexible diaphragm into the device also combines several advantages: thus, as mentioned above, a defined volume of liquid can be extruded and processed by utilizing the targeted offset of the diaphragm towards a defined opening in the device. Furthermore, the use of a flexible diaphragm allows the liquid to be almost completely contained within the device during processing, requiring only a vent. This advantageously prevents sample contamination of the environment, or vice versa. Furthermore, such microfluidic lab-on-a-chip tubes can be manufactured inexpensively from polymers using mass production methods such as injection molding or laser transmission welding.

[0013] According to another embodiment, the valve can be constructed based on a diaphragm. For example, diaphragm-based valves can be used, particularly for controlling fluid transport within pressure-based microfluidic devices. Here, the flow rate through the microfluidic channel can be controlled by offset of the flexible diaphragm onto the valve insert. For this purpose, suitable surface properties of the material, such as a defined surface roughness, are necessary to achieve the best possible seal using such a diaphragm-based microfluidic valve. Advantageously, diaphragm-based valves can be manufactured cost-effectively and used to guide fluid within the device.

[0014] According to another embodiment, the valve can include an actuation channel for controllably deflecting a diaphragm into a valve cavity. For example, the microfluidic valve can be switched on and off via a pressure-based deflection of an elastic diaphragm into a valve cavity, wherein pressure can be applied to the diaphragm via a pneumatic actuation channel. This has the advantage that the valve can be precisely controlled.

[0015] According to another embodiment, the valve pre-channel can have a length of 0.5 mm to 10 mm, and as a supplementary or alternative solution, it can have a length of 100 x 100 μm. 2 Up to 3x3mm 2The cross-section can be adjusted, and as a supplementary or alternative, it can have a volume of 100 nml to 5 μl. Advantageously, such a size ratio allows the use of capillary forces present within the valve pre-channel to induce capillary stabilization of the phase interface geometry as the liquid enters the valve pre-channel. The width, or cross-sectional dimension, of the valve pre-channel is particularly smaller than the capillary length of the liquid used. In another embodiment, the width of the valve pre-channel is 0.1 to 1.5 times, preferably 0.2 to 1.0 times, and particularly preferably 0.2 to 0.5 times, the capillary length of the liquid, in order to achieve reliable stabilization of the phase interface geometry between the liquid and gas volumes on the one hand, and easy manufacturability of the device on the other hand, as well as low fluid resistance when pumping the liquid through the valve pre-channel.

[0016] According to another embodiment, the device can include another valve pre-channel, which is fluidly connected to another supply channel via another channel engagement and, as a supplement or alternative, to another first output channel. This other valve pre-channel can be arranged between the other valve and the other channel engagement, and in the device's ready-to-operate state, it can include a gas volume for shielding the other valve relative to the liquid. For example, the device can include multiple functional units for processing sample materials, where each unit can be separated from another unit via a valve and a valve pre-channel. For example, the other valve pre-channel can be correspondingly arranged in a similar location within the microfluidic network as the valve pre-channel. This has the advantage of allowing different processes to be performed sequentially, for example, with different liquids within the device, where negative impacts on each process can be avoided.

[0017] Furthermore, a variation of the method for operating the microfluidic device described above is proposed, wherein the method includes the step of closing the valve and the step of introducing liquid into the supply channel, and preferably into the valve pre-channel, wherein the liquid is blocked relative to the valve due to the gas volume. As explained above, the gas volume advantageously prevents the liquid from contacting the valve. Especially when there is no gas volume in the valve pre-channel, according to the specific design of the method, the gas volume can be introduced into the valve pre-channel before the liquid is introduced.

[0018] According to one embodiment, during the closing step, pressure, particularly overpressure, can be applied to the diaphragm of the valve to close it. For example, the valve can be operated via the control channel, wherein closing the valve can be achieved by applying overpressure to the control channel. Advantageously, this allows for controlled offset of the diaphragm and thus controlled closing of the valve.

[0019] According to another embodiment, in the introduction step, pressure, especially overpressure, can be applied to the storage chamber storing the liquid to introduce the liquid into the supply channel. For example, the liquid can be stored in the storage chamber until, for example, it is needed for transporting sample material. Thus, the liquid can advantageously be introduced into the microfluidic channel system at any time and as needed. As a supplement or alternative, the liquid can be drawn from the storage chamber and introduced into the microfluidic channel system by generating negative pressure in the microfluidic channel system.

[0020] According to another embodiment, the method can include a step of outputting the liquid through a first output channel, wherein the gas volume can be compressed in the introduction step and expanded in the output step. For example, the pressure can be increased by means of a pumping process in the microfluidic device, the pressure being transmitted by the inflowing liquid. Therefore, liquid can enter the valve pre-channel. Here, the air volume in the valve pre-channel can be compressed, creating a back pressure. Preferably, when the liquid enters the valve pre-channel, an interface with a shape particularly stable by capillary forces is formed between the gas volume and the liquid in the valve pre-channel. After a short time, the liquid can continue to move through the microfluidic network along the open path, i.e., along the first output channel, and the existing hydraulic pressure can drop again. Through the decrease in pressure exerted by the inflowing liquid, the capacity effect of the gas volume in the valve pre-channel can now be utilized: the previously existing back pressure formed by the gas volume can also be relaxed, and the liquid that previously entered the valve pre-channel can be completely expelled from the valve pre-channel. Preferably, the liquid squeezed into the valve pre-channel is completely squeezed out of the valve pre-channel by means of an interface preferably constructed in the valve pre-channel and stabilized by capillary force between the liquid and gas volumes. Thus, the valve pre-channel can be used in a particularly advantageous manner for many such pumping processes without undesirable seal leakage of the valve downstream of the valve pre-channel.

[0021] According to another embodiment, the method can include a valve-opening step. For example, if the process is to be carried out in a pre-separated unit of the microfluidic system using a valve, the valve can be opened. The pneumatic control channel can, for example, be arranged on the hydrodynamically opposite side of the diaphragm. Therefore, pressure, especially overpressure, is required to press the valve diaphragm against the valve tabs and close the valve. Advantageously, the liquid can then be guided through a pre-channel and a second output channel for processing in a pre-separated unit of the microfluidic system.

[0022] The method can be implemented, for example, in software, hardware, or a hybrid of software and hardware, such as in a control device. Attached Figure Description

[0023] Embodiments of the scheme described herein are shown in the accompanying drawings and explained in more detail in the following description. Wherein:

[0024] Figure 1 A schematic top view of one embodiment of a microfluidic device with a valve pre-channel is shown;

[0025] Figure 2 A schematic side view of one embodiment of a microfluidic device with a valve pre-channel is shown;

[0026] Figure 3 A schematic top view of one embodiment of a microfluidic device with a valve pre-channel is shown;

[0027] Figure 4 A schematic top view of one embodiment of a microfluidic device with a valve pre-channel is shown;

[0028] Figure 5 A perspective side view of one embodiment of a microfluidic device with a valve pre-channel is shown;

[0029] Figure 6 A top view of an embodiment of a microfluidic device with a valve pre-channel is shown in operation;

[0030] Figure 7 A top view of an embodiment of a microfluidic device with a valve pre-channel is shown in operation;

[0031] Figure 8 A top view of an embodiment of a microfluidic device with a valve pre-channel is shown in operation;

[0032] Figure 9 A schematic top view of one embodiment of a microfluidic device is shown.

[0033] Figure 10 A flowchart of a method for operating a microfluidic device according to one embodiment is shown;

[0034] Figure 11 A flowchart of a method for operating a microfluidic device according to one embodiment is shown; and

[0035] Figure 12 A schematic diagram of one embodiment of an analytical apparatus for receiving a microfluidic device is shown. Detailed Implementation

[0036] In the following description of advantageous embodiments of the invention, the same or similar reference numerals are used for elements shown in different figures and that serve similar functions, wherein repeated descriptions of these elements are omitted.

[0037] Figure 1 A schematic top view of one embodiment of a microfluidic device 100 having a valve pre-channel 105 is shown. The prominent feature of the device 100 shown here is a supply channel 110 for guiding liquid 112 and a first output channel 115 for further guiding liquid 112, wherein the supply channel 110, the first output channel 115, and the valve pre-channel 105 are fluidly connected to each other via a channel engagement 117. For illustrative purposes only, the valve pre-channel 105 is arranged perpendicular to the supply channel 110 and the first output channel 115. Furthermore, the device 100 includes a second output channel 120, in this embodiment of which the second output channel can be separated from the valve pre-channel 105 by a diaphragm-based microfluidic valve 125, for illustrative purposes only. In other words, the valve pre-channel 105 of the capillary is arranged between the valve 125 and the transition position between the supply channel 110 and the first output channel 115.

[0038] As an example only, in this embodiment, the microfluidic channels such as the valve pre-channel 105, the supply channel 110, and the first and second output channels 115, 120 have a diameter of 600 × 400 μm. 2 The cross-section. In another embodiment, the channel can have a cross-section of 100 × 100 μm. 2 Up to 3×3mm 2 Preferred size: 300×300μm 2 Up to 1×1mm 2 The cross-section. Here, the liquid 112 is, for example, water, and the capillary length... At a temperature of 20℃ and a surface tension, or surface energy, of γ = 0.073 J / m 2 The density is ρ = 10 3 kg / m 3And the acceleration due to gravity is g = 9.81 m / s². 2 In the case of l kap = 2.7 mm. The capillary length is... It is defined as the square root of the quotient of the product of surface energy on one side and density and gravitational acceleration on the other side. Therefore, the ratio of the maximum width of the valve pre-channel 105 to the capillary length of the liquid 112 is: 0.6mm / 2.7mm = 2 / 9 = 0.22.

[0039] By using liquid 112, such as an aqueous solution containing detergent, or by increasing the temperature, the surface tension of the liquid can be reduced, thereby reducing the capillary length. To achieve reliable stability of the phase interface in the valve pre-channel 105, the capillary length should be particularly greater than the maximum width of the valve pre-channel, that is... Therefore, at a density of ρ = 10 3 kg / m 3 And the acceleration due to gravity is g = 9.81 m / s². 2 In this case, the surface tension should be at least 0.0036 J / m. 2 That is, γ≥0.0036J / m 2 .

[0040] In this embodiment, the valve pre-channel 105 is formed with a length of 4 mm and a volume of 1 μl, which is merely an example. In another embodiment, the valve pre-channel can have a length of 0.5 mm to 10 mm, preferably 1 mm to 5 mm, and a volume of 100 nml to 5 μl, preferably 500 nml to 2.5 μl. In one embodiment, the valve 125 is configured with an effective displacement volume of 125 nml, which is merely an example. In another embodiment, the valve 125 can have a displacement volume of 80 nml to 1 μl, preferably 100 nml to 300 nml.

[0041] In the accompanying drawings shown here, the device 100 is illustrated in a ready-to-operate state, and the valve pre-pass 105 includes a gas volume 130, which can also be referred to as a gaseous medium. In this embodiment, the gas volume 130 is merely exemplarily air, which acts as a volumetric capacity relative to pressure fluctuations.

[0042] Furthermore, in the illustration shown here, liquid 112 is guided into the supply channel 110 and the first output channel 115, wherein the liquid 112 is partially squeezed into the valve pre-channel 105 adjacent to the channel junction 117. In this embodiment, the liquid 112 is an aqueous solution for transporting sample material. In another embodiment, the apparatus can process aqueous solutions, such as buffer solutions containing components of the sample substance, mineral oil, silicone oil, or fluorinated hydrocarbons. In this embodiment, the liquid 112 here has a capillary phase interface 135 relative to the gas volume 130.

[0043] The diaphragm-based microfluidic valve 125 is closed. That is, in this embodiment, the diaphragm of the microfluidic valve 125 is pressed against the valve plate by pneumatically applied pressure to achieve a seal. Therefore, in this embodiment, the opening and closing of the microfluidic valve 125 is achieved by pressure-based offset of the elastic diaphragm into the valve gap 140, wherein the pressure can be applied to the diaphragm via a pneumatically operated channel 145, which is merely an example of this.

[0044] When valve 125 is closed and liquid 112 is partially forced into valve pre-passage 105, gas volume 130 fills the section of valve pre-passage 105 adjacent to valve 125. Here, gas volume 130 at least partially and completely fills valve pre-passage 105, i.e., across the entire cross-section of valve pre-passage 105. In this way, valve 125 is reliably isolated from liquid 112. Only when valve 125 is opened can gas volume 130 escape through valve 125, allowing liquid 112 to advance into and through valve 125 until valve 125 is closed again.

[0045] Figure 2 A schematic side view of one embodiment of a microfluidic device 100 having a valve pre-channel 105 is shown. The device 100 and the valve pre-channel 105 shown here correspond to or are similar to the device and valve pre-channel depicted in the previous figures. In this embodiment, the device 100 is constructed of a total of four polymer layers. Two layers 201 and 203 are merely exemplary two rigid injection-molded polymer components containing fluid and pneumatic microchannels. The layer disposed therebetween is implemented by an elastic diaphragm 202, toward which pressure can be locally applied by means of a pneumatically actuated channel to deflect the elastic diaphragm into a void and thus create and / or control liquid transport within the device 100. In this embodiment, the controlled deflection of the layer constituting the diaphragm 202 into the valve void 140 is correspondingly achieved by the pneumatically actuated channel 145 disposed on the valve 125. The fourth layer 204 is merely exemplary implemented as a polymer membrane for sealing the microchannels present in layer 203. In an advantageous embodiment, the individual layers 201, 203, 204 and the film 202 are alternately optically transparent and absorbent, so that the layers can be easily and cost-effectively joined by means of laser transmission welding.

[0046] The valve 125 in Figure 2 The form shown is merely an example and has been selected. The valve 125 can also be implemented in other forms suitable for microfluidic systems.

[0047] Figure 3 and Figure 4 Schematic top views of one embodiment of a microfluidic device 100 having a valve pre-channel 105 are shown. The device 100 and valve pre-channel 105 shown here correspond to or are similar to the device and valve pre-channel depicted in the previous figures. In detail, Figure 3 A cut-off portion of the top view showing the illustrated flow direction 300 is shown, and Figure 4 A top view showing a depicted liquid path 400 is shown. Figure 3 Compared to a larger cut-off portion.

[0048] As in Figure 3 The arrow shown in the illustration, indicating the flow direction 300, is as described above. Figure 1 The same liquid as depicted can be introduced through the supply channel 110 and discharged through the first output channel 115. At the channel junction 117, or at the intersection of the supply channel 110 and the first output channel 115, the valve pre-channel 105 is arranged in the straight extension of the supply channel 110, thus forming a T-shaped, right-angled connection between the supply channel 110, the first output channel 115, and the valve pre-channel 105 in this embodiment. A diaphragm-based microfluidic valve 125, merely exemplary, is arranged at the end of the valve pre-channel 105 opposite to the channel junction 117, separating the valve pre-channel 105 from the second output channel 120 located behind it. Therefore, compared to the preceding... Figure 1 Unlike the embodiments described herein, in this embodiment, the positions of the first output channel 110 and the valve pre-channel 105 are interchanged. Therefore, a 90° deflection of the liquid flow is achieved at the T-shaped intersection formed by the supply channel 110, the valve pre-channel 105, and the first output channel 115, as by... Figure 3 As shown by the arrows illustrated. Accordingly, the deflection of the liquid flow is specifically achieved through the interaction of the liquid with the gas volume enclosed in the valve pre-passage 105. A larger section of the liquid path 400 used is in Figure 4 The arrows are used to mark the characters.

[0049] Figure 5A perspective side view of one embodiment of a microfluidic device 100 having a valve pre-channel 105 is shown. The device 100 and the valve pre-channel 105 shown here correspond to or are similar to the device and valve pre-channel depicted in the previous figures. Here, the accompanying drawings show, in perspective view, the three-dimensional construction of the microfluidic valve and the implementation of fluidic and pneumatic microchannels at two different levels.

[0050] Figure 6 , Figure 7 and Figure 8 Top views of an embodiment of a microfluidic device 100 having a valve pre-channel 105 in operation are shown. The device 100 and the valve pre-channel 105 shown here correspond to or are similar to the device and valve pre-channel depicted in the previous figures. Here, these three figures correspond to one implementation of an embodiment in the form of a polymer multilayer structure as described above. Figure 4 The cut-off portion shown is shown.

[0051] Figure 6 , Figure 7 and Figure 8 The different illustrations show the trajectory of liquid 600 at three different moments during the pumping process. For better contrast, liquid 600 is doped with fluorescent pigment to make it more visible or describable. Figure 6 The scaling bar 605 in the diagram merely corresponds to a length of 5mm as an example. These three diagrams represent the sequential process, where... Figure 6 Corresponding to time t1, Figure 7 Corresponding to time t2, and Figure 8 This corresponds to time t3, where t3 > t2 > t1. These three figures show how the stained liquid 600 moves along... Figure 4 The path depicted is pumped through the microfluidic network. This is evident in the three figures from the following perspective: Figure 6 Only about one-third of the path shown in the first example is wetted by liquid 600. Figure 7 About two-thirds of it was wetted by liquid 600 and finally in Figure 8 The entire path is wetted by the colored liquid 600.

[0052] In this embodiment, the pumping process can be implemented using the pump chamber of device 100. Liquid is repeatedly drawn into the pump chamber through the inlet valve and then discharged through the outlet valve, thereby progressively wetting the illustrated path of the microfluidic network with liquid 600. During this pumping process, a rise in hydraulic pressure occurs in the microfluidic system, particularly during liquid discharge. Simultaneously, the liquid moves through the microfluidic system along a switched path. The pressure rise in the microfluidic system associated with the discharge process from the pump chamber advantageously utilizes the current valve pre-channel 105. This... Figure 6 , Figure 7 and Figure 8 The following description is provided with the aid of enlarged cropped portions from three figures, which respectively show the device 100 in an enlarged manner. Figure 6 The area is marked by a rectangular box with dashed lines. It shows the state of the valve 125, valve pre-pass 105, and passage engagement 117 during the pumping process.

[0053] exist Figure 6 In this process, the valve pre-channel 105 is first filled with a gas volume 130, which is, for example, air, and the interface with respect to the liquid 600 is directly disposed at the channel junction 117 adjacent to the valve pre-channel 105, which is, for example, formed as a T-shaped intersection. Figure 7 The diagram illustrates the period of pumping shock. The pressure in the microfluidic system, that is, especially the pressure transmitted by the inflowing liquid 600, is compared with... Figure 6 The situation shown in the diagram is improved. Therefore, liquid 600 is partially disposed in the valve pre-passage 105. Here, the gas volume 130 in the valve pre-passage 105 is compressed, creating a back pressure. This back pressure and the volume effect of the valve pre-passage 105 prevent the incoming liquid 600 from advancing all the way to the microfluidic valve 125 located downstream of the valve pre-passage 105. Possible seal permeation of the merely exemplary diaphragm-based valve 125 is correspondingly prevented.

[0054] exist Figure 7 Following the pumping impact shown, the liquid 600 continues to move along the open path through the microfluidic network, and the existing hydraulic pressure decreases again. This state occurs... Figure 8As shown in the diagram, the volumetric effect of the air-filled space in the valve pre-channel 105 is realized through the decrease in pressure exerted by the inflowing liquid 600. The counter-pressure previously present in the valve pre-channel 105, formed by the air, is relaxed, and the liquid 600 previously entering the valve pre-channel 105 is completely expelled from the valve pre-channel. This is achieved, in particular, through the capillary stability associated with the surface tension of the entering liquid 600 and the geometry of the phase interface. Furthermore, in this embodiment, the surface properties of the valve pre-channel 105 are configured only, by way of example, hydrophobic, so that no liquid film caused by capillary forces remains in the valve pre-channel 105. Thus, in a particularly advantageous manner, the valve pre-channel 105 can be used in large-volume pumping processes without undesirable seal permeation of the subsequent valve 125. In another embodiment, the valve pre-channel can also be configured to be slightly hydrophilic.

[0055] Figure 9A schematic top view of one embodiment of a microfluidic device 100 is shown. The device 100 shown herein corresponds to or is similar to the device depicted in the previous figures. In this embodiment, the device 100 includes a microfluidic network 900 consisting of different microfluidic channels, chambers, and valves. In this embodiment, the network 900 has four functional units 901, 902, 903, and 904, which are shown by way of dashed lines. The various functional units 901, 902, 903, and 904 are merely exemplary in that they can be used, particularly continuously, i.e., sequentially, when implementing a microfluidic test procedure within the microfluidic network 900, wherein different liquid solutions can be used in different steps of the microfluidic test procedure. The liquid can be, merely exemplary, pre-stored in a storage chamber 905 and introduced into the network by applying overpressure to the storage chamber 905. To prevent undesirable mixing of different liquid solutions, the functional units 901, 902, 903, and 904 can be separated from each other by microfluidic valves. Therefore, the first functional unit 901 can be exemplarily separated from the second functional unit 902 by a valve 125 arranged on the valve pre-passage 105. In this embodiment, the other functional unit 902 includes another valve pre-passage 910, which is exemplarily fluidly connected to another supply passage 920 and another first output passage 925 via another passage engagement 915. Here, the other valve pre-passage 910 is arranged between another valve 930 and another passage engagement 915, wherein in this embodiment, the other valve 930 is configured to separate the second functional unit 902 from the third functional unit 903. Exemplarily, the other valve pre-passage 910 is configured identically to the valve pre-passage 105 to include a gas volume for shielding the other valve 930 relative to the liquid in the ready-to-operate state of the device 100. In this embodiment, all functional units 901, 902, 903, and 904 of the device 100 are configured in a manner that allows them to be separated from each other. As an example only, the device 100 described in this embodiment is formed with dimensions of 186x78mm. 2 The overall lateral dimensions. In another embodiment, the device can have a size of 75x25mm. 2 Up to 300x200mm 2 100x50 mm is preferred. 2 Up to 200x100mm 2The overall size. Here, in this embodiment, the pressure differential (overpressure or negative pressure) that can be applied by means of a pump chamber to generate microfluidic flow by means of an exemplary expulsion or suction is 700 mbar. In another embodiment, a pressure differential of 100 mbar to 2000 mbar, preferably 400 mbar to 1500 mbar, can be applied to the device. In this embodiment, the microfluidic device 100 is particularly manufactured from polymers, such as polycarbonate (PC) and thermoplastic polyurethane (TPU), using mass production methods, such as injection molding, stamping, and laser transmission welding. In other embodiments, the device can be manufactured using polystyrene (PS), styrene-acrylonitrile copolymer (SAN), polypropylene (PP), polyethylene (PE), cyclic olefin copolymers (COP, COC), polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), or thermoplastic elastomers (TPE), such as styrene block copolymers (TPS).

[0056] Figure 10 A flowchart of a method 1000 for operating a microfluidic device according to one embodiment is shown. The device capable of being operated by this method corresponds to or is similar to the device depicted in the previous figures. The method 1000 includes a step 1005 of closing a valve of the device and a step 1010 of introducing liquid into a supply channel, wherein the liquid is blocked relative to the valve due to gas volume.

[0057] In another embodiment, the device can be configured without a pre-channel valve. Here, for example, due to manufacturing tolerances, incomplete dissipation of the liquid in the valve region may occur, thereby leaving a liquid film in a portion of the microfluidic valve, which causes seal permeation. Seal permeation may also occur by means of capillary-induced surface wetting, especially in cases where the liquid used has a high affinity for surfaces due to similar polarity. Furthermore, in a device formed without a pre-channel valve, seal permeation and leakage of liquid may occur if the hydraulic pressure applied to the valve by the liquid exceeds the pneumatic pressure pressing the valve diaphragm onto the valve tabs, particularly for a very short time. Seal permeation may also occur if, in an embodiment without a pre-channel valve, inertial forces, i.e., particularly the pulse transmission applied to the valve diaphragm by the heavier mass of the liquid, exceed, for a very short time, the reaction force exerted by the diaphragm on the liquid due to the pneumatic pressure applied to the diaphragm.

[0058] In the embodiments shown here, the pre-channeling of the valve prevents seal penetration of the microfluidic valve, which has a beneficial effect on the performance and reliability of the microfluidic system.

[0059] Figure 11A flowchart of a method 1000 for operating a microfluidic device according to one embodiment is shown. The method 1000 shown herein corresponds to or is similar to the one described above. Figure 10 The method described herein differs in that the embodiment shown here has additional steps. In this embodiment, in the closing step 1005, overpressure is applied to the diaphragm of the valve to close it. In the subsequent introducing step 1010, overpressure is applied, merely exemplarily, to the storage chamber storing the liquid to introduce the liquid into the supply channel. In this embodiment, after the introducing step 1010, a step 1100 is performed to output the liquid through a first output channel. Here, a gas volume is present in the valve pre-channel, the volumetric effect of which prevents wetting of the subsequent microfluidic valve. In this embodiment, the gas volume is compressed in the introducing step 1010 and expanded in the output step 1100. In this embodiment, the introducing and discharging steps 1010 and 1100 are performed alternately, i.e., repeatedly, to deliver larger volumes of liquid through the microfluidic network and / or pump different liquid solutions through the microfluidic network. After the output step 1100, the method 1000 merely exemplarily includes the valve opening step 1105.

[0060] Figure 12 A schematic diagram of one embodiment of an analytical device 1200 for receiving a microfluidic device is shown. The analytical device 1200 is merely exemplarily configured to receive, via an input opening 1205, a device as shown in the diagram. Figures 1 to 9 The microfluidic device described herein is used to perform analytical processes within the device. In this embodiment, the analytical device 1200 includes a control device 1210 configured to control the device in front of it. Figure 10 and 11 The steps of the method described in the document.

Claims

1. A microfluidic device (100), wherein the device (100) has the following characteristics: A supply channel (110) for guiding liquid (112), wherein the supply channel (110) extends into a channel engagement portion (117); A first output channel (115) for further guiding liquid (112), wherein the first output channel (115) is fluidly connected to the supply channel (110) via the channel engagement portion (117); A valve pre-channel (105) for further guiding liquid (112), wherein the valve pre-channel (105) is fluidly connected to the supply channel (110) via the channel engagement portion (117); and Valve (125), the valve being arranged between the valve pre-passage (105) and the second output passage (120); Its features are, The valve pre-channel (105) includes a gas volume (130) for shielding the valve (125) relative to the liquid (112) in the ready-to-operate state of the device (100). The width of the valve pre-channel (105) is less than or equal to 1.5 times the capillary length of the liquid (112) in the device (100).

2. The microfluidic device (100) according to claim 1, wherein the width of the valve pre-channel (105) is less than or equal to 1.5 times the capillary length of the liquid (112) in the supply channel (110).

3. The microfluidic device (100) according to claim 1, wherein the width of the valve pre-channel (105) is less than the capillary length of the liquid (112) in the device (100).

4. The microfluidic device (100) according to claim 1, wherein the width of the valve pre-channel (105) is smaller than the capillary length of the liquid (112) in the supply channel (110).

5. The microfluidic device (100) according to claim 1, wherein the width of the valve pre-channel (105) is the maximum lateral extension of the cross-section of the valve pre-channel (105).

6. The microfluidic device (100) according to any one of claims 1 to 5, wherein the valve (125) is configured to separate the valve pre-channel (105) from the second output channel (120).

7. The microfluidic device (100) according to any one of claims 1 to 5, wherein the valve pre-channel (105) is arranged substantially perpendicular to the supply channel (110) and / or the first output channel (115).

8. The microfluidic device (100) according to any one of claims 1 to 5, wherein the valve pre-channel (105) is hydrophobically configured, and the supply channel (110) and / or the first output channel (115) is hydrophilically configured.

9. The microfluidic device (100) according to any one of claims 1 to 5, wherein the device (100) is configured as a pressure-based system.

10. The microfluidic device (100) according to any one of claims 1 to 5, wherein the valve (125) is configured based on a diaphragm.

11. The microfluidic device (100) according to any one of claims 1 to 5, wherein the valve (125) includes an actuation channel (145) for controlled offset of the diaphragm (202) into the valve gap (140).

12. The microfluidic device (100) according to any one of claims 1 to 5, wherein the valve pre-channel (105) has a length of 0.5 mm to 10 mm and / or 100 x 100 μm. 2 Up to 3x3mm 2 The cross-section and / or volume of 100 nml to 5 μl.

13. The microfluidic device (100) according to any one of claims 1 to 5, having another valve pre-channel (910) fluidly connected to another supply channel (920) and / or another first output channel (925) via another channel engagement (915), wherein the other valve pre-channel (910) is arranged between another valve (930) and the other channel engagement (915), and wherein the other valve pre-channel (910) includes a gas volume (130) for shielding the other valve (930) relative to the liquid (112) in a ready-to-operate state of the device (100).

14. A method (1000) for operating a microfluidic device (100) according to any one of claims 1 to 13, wherein the method (1000) comprises the following steps: Close the valve (125); and Liquid (112) is introduced into the supply channel (110), wherein the liquid (112) is blocked relative to the valve (125) due to the gas volume (130).

15. The method (1000) according to claim 14, wherein pressure is applied to the diaphragm (202) of the valve (125) in the closing step to close the valve (125).

16. The method (1000) according to claim 14 or 15, wherein pressure is applied to the storage chamber (905) storing the liquid (112) in the introduction step to introduce the liquid (112) into the supply channel (110).

17. The method (1000) according to claim 14 or 15, comprising the step of outputting the liquid (112) through the first output channel (115).

18. The method (1000) of claim 17, wherein the gas volume (130) is compressed in the introducing step and expanded in the output liquid step.

19. The method (1000) according to claim 14 or 15, wherein an interface having a shape stabilized by capillary force is formed between the gas volume (130) and the liquid (112) in the valve pre-passage (105).

20. The method (1000) according to claim 19, wherein the interface causes, in the step of outputting the liquid, to cause the liquid (112) that was injected into the valve pre-channel (105) in the step of introduction to be extruded from the valve pre-channel (105).

21. The method (1000) according to claim 20, wherein the interface causes complete extrusion of the liquid (112) that was squeezed into the valve pre-channel (105) in the step of outputting the liquid during the step of introduction from the valve pre-channel (105).

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