Microfluidic receiving element for a microfluidic device for processing fluids, microfluidic device, and method for producing a microfluidic receiving element

Abstract

The invention relates to a microfluidic receiving element (110) for a microfluidic device (100) for processing fluids. At least one recess (115) for receiving a sample liquid is provided on the plane of the upper face (130) of the receiving element (110). At least sections of the surface (200) of the recess (115) have a hydrophilic layer (205). Additionally, at least sections of the surface (200) of the recess (115) have a hydrophobic layer (210).

Description

[0001] Description

[0002] title

[0003] Microfluidic receiving element for a microfluidic device for processing fluids, microfluidic device and method for producing a microfluidic receiving element

[0004] State of the art

[0005] The approach presented is based on a microfluidic receiving element for a microfluidic device for processing fluids, a microfluidic device, and a method for producing a microfluidic receiving element according to the preamble of the independent claims. The approach presented also relates to a computer program.

[0006] Conventional biological analysis devices can often only test a sample fluid for one pathogen or virus, for example, in a single analysis run. Using a silicon array (also called a Si array), i.e., an arrangement of a plurality of recesses – also called wells or cavities – on a silicon chip, which is incorporated into a cartridge for a biological analysis device, a plurality of detection reactions, particularly for different pathogens, can run in parallel through a plurality of separate, enclosed reaction volumes. For this purpose, reagents can be pre-stored in individual wells in the correct quantities. This can be achieved, for example, using a spotting process.The chip can then be installed in a flow cell or cartridge, and during use, the sample fluid, the analyte, can flow over it, particularly parallel to the chip surface, thus filling individual wells with the analyte. The individual wells can then be fluidically separated from each other, and the detection reactions can run in parallel, particularly in the now-closed reaction volumes.

[0007] Revelation of the approach presented here

[0008] Against this background, the approach presented here provides a microfluidic receiving element, a microfluidic device with a receiving element, and a method for producing a microfluidic receiving element, as well as a control device using this method, a corresponding computer program, and finally a corresponding machine-readable storage medium according to the main claims. The measures listed in the dependent claims enable advantageous refinements and improvements of the receiving element specified in the independent claim.

[0009] The microfluidic receiving element presented here can advantageously reduce pinning (“sticking”) occurring at the edges of cavities in a microfluidic device, so that the filling behavior of the cavity can be improved.

[0010] A microfluidic receiving element for a microfluidic device for processing fluids is presented. At least one recess for receiving a sample liquid is arranged in a plane of a top side of the receiving element. A surface of the recess at least partially comprises a hydrophilic layer. The surface of the recess further comprises at least partially a hydrophobic layer.

[0011] The recess can alternatively be referred to as a well or a cavity. The layer can also be referred to as a coating.

[0012] The approach presented here includes a new arrangement for the production of a microfluidic receiving element, whereby such a production can offer advantages of good fillability of the recess through an adapted geometry or coating of the recess and / or advantages of minimized carryover.

[0013] A hydrophobic layer in a portion of the well, for example, near the well bottom, where a reagent can be deposited during spotting, can prevent the reagent from experiencing capillary action, i.e., from being drawn up into a corner or corners of the well. This design thus offers the advantage that the reagent is less likely to be carried over and / or washed out in a subsequent fluidics step.

[0014] A particularly advantageous embodiment of the approach presented here is one in which the recess in the plane of the upper side of the receiving element has at least partially an angular geometry and / or shape. In particular, by providing an angular geometry of the recess, a wave front of this sample solution can be broken at corners of the recess's geometry when the aqueous solution, also referred to as sample liquid, is introduced. This allows, in conjunction with the introduced hydrophobic layer, the recess to be filled with the sample liquid or aqueous solution with little or no rinsing of material or reagents in the recess.A further advantage of this embodiment and in particular an advantage of the angular geometry is that pinning, i.e. “attaching”, of a phase boundary, i.e. a liquid front, to an edge of the recess can be prevented or reduced in a particularly efficient manner, so that the filling behavior of the recess can be improved.

[0015] However, the well geometries pose a challenge, as the sharp points / corners (albeit possibly slightly rounded) can extend to the bottom of the well - also called the bottom of the well or well base. Capillary forces could cause liquids (e.g. reagents previously deposited / spotted there) to be drawn up into the corners on the bottom of the well. The capillary forces and / or the height to which the liquid can be drawn up can depend on the radius of curvature of the corners (the smaller the radius of curvature, the greater the force). When another liquid (e.g. the sample liquid) flows over the wells, substances drawn up in the corners could be picked up and transported to neighboring wells. Such carryover can lead to cross-contamination and, in subsequent diagnostics, to incorrect diagnostics.For example, cross-contamination can lead to a chemical and / or biochemical reaction not proceeding in a cavity because a reactant is no longer present in the required amount and / or an additional reactant (from an adjacent cavity) is present that can inhibit, i.e., hinder, a reaction. Alternatively, an incorrect reaction can occur in a cavity because, in particular, a chemical other than the original one might be present in that cavity. All of this can lead to a malfunction (for example, a false positive and / or false negative).

[0016] According to a further embodiment, the hydrophobic layer can be arranged on a bottom of the recess and / or at least on a partial region of at least one side wall of the recess. A hydrophobic layer of a partial region of the well near the well bottom, at or on which a reagent can be deposited during spotting, can prevent the reagent from experiencing a capillary effect, i.e., from being drawn up, for example, into a corner or corners of the well. This embodiment thus offers the advantage that the reagent is less likely to be carried over and / or washed out in a subsequent fluidics step.

[0017] According to one embodiment, the surface of the recess can be exposed on the side wall of the recess in a free area between the hydrophobic layer and the hydrophilic layer. This is advantageous in that contact between the hydrophilic layer and the hydrophobic layer can be avoided.

[0018] According to a further embodiment, the hydrophobic layer on the side wall of the recess, i.e. on the side wall of the well, i.e. on the well wall, can have a larger surface area than the hydrophilic layer. If the surface area of ​​the hydrophobic layer is too small, the spotted reagent could come into contact with the hydrophilic layer, which could induce a capillary effect. In such a case, the reagent could pull itself up at least one side wall of the well. If the surface area of ​​the hydrophobic layer is too large, for example, down to below an upper edge of the well, filling of the well can be hindered. Ideally, the height of the surface of the hydrophobic layer in an at least approximately vertical direction from the well bottom to the hydrophilic layer is slightly greater than the (later) filling height of the (spotted) reagent.For example, such a height of the surface of the hydrophobic layer can correspond to the filling height of the (spotted) reagent times 1.1.

[0019] According to one embodiment, the height of the hydrophobic layer can be less than the height of the recess. In this case, the height of the hydrophobic layer can be greater than the height of the hydrophilic layer on the side wall of the recess. The height up to which the recess, i.e., the well wall, is hydrophobic can be variable, but the height of the hydrophobic layer is usually less than the height of the recess. If the height of the hydrophobic layer is too low, the spotted reagent could come into contact with the hydrophilic layer, which could trigger a capillary effect. In such a case, the reagent could pull itself up the side wall of the recess, which is to be avoided. If the height of the hydrophobic layer is too high, for example, below an upper edge of the recess, filling the recess can be hindered. Ideally, the height of the hydrophobic layer is slightly greater than the (later) fill level of the (spotted) reagent.For example, the height of the hydrophobic layer can be equal to the filling height of the (spotted) reagent times 1.1.

[0020] According to a further embodiment, the hydrophilic layer can be arranged on the upper side of the receiving element and / or at least on a partial region of the side wall and / or between the hydrophobic layer and the bottom of the recess. This means that the upper side of the receiving element has at least largely hydrophilic surface properties. A hydrophilic surface property can be understood as a relationship in which the contact angle of a water droplet on a surface is less than 90 degrees, preferably less than 60°, even better less than 50°. In the present case, this can particularly be the surface of the receiving element. This embodiment is advantageous in that the hydrophilic layer can promote or ensure advantageous filling of the recess.

[0021] According to one embodiment, a reagent for conducting an analytical reaction with the sample liquid can be stored in the recess. This can increase the efficiency of a chemical or biochemical detection reaction conducted in the recess, which in turn can optimize chemical and / or biochemical analysis processes.

[0022] According to a further embodiment, at least one further recess for receiving a sample liquid can be arranged in the plane of the upper side of the receiving element. A surface of the further recess can at least partially comprise the hydrophilic layer or a further hydrophilic layer. The further recess can at least partially have an angular geometry and / or shape in the plane of the upper side of the receiving element. This embodiment is advantageous in that the hydrophilic layer can promote or ensure advantageous filling of the recess and / or the further recess.A further advantage of this embodiment, and in particular an advantage of the angular geometry, is that pinning, i.e., "adhering," of a phase interface, i.e., a liquid front, to an edge of the recess and / or to an edge of the further recess can be prevented or reduced in a particularly efficient manner, so that the filling behavior of the recess and / or the further recess can be improved. In other words, the at least partially angular geometry of the recess and / or the at least partially angular geometry of the further recess can promote the fillability of the recess.

[0023] In particular, by using the additional recess, the efficiency of a chemical or biochemical detection reaction carried out in the recess can be increased, which in turn can optimize chemical and / or biochemical analysis processes. Furthermore, by using the additional recess, a plurality of chemical and / or biochemical detection reactions can be carried out in parallel or simultaneously using the receiving element. This, in turn, has the advantage of increasing the effectiveness of the final product and, at the same time, saving time and costs in production through parallel processing.

[0024] Furthermore, a microfluidic device for processing fluids is presented, using a variant of the previously presented microfluidic receiving element. The device can be, for example, a lab-on-chip cartridge. The combination of the microfluidic device with the receiving element has the advantage that many of the previously described advantages for processing a fluid or for analyzing sample components dissolved in the fluid can be optimally implemented. In particular, the advantages of good fillability can be combined with an adapted geometry while simultaneously minimizing carryover and optimizing analysis processes. In this way, for example, the efficiency of a biochemical detection reaction carried out in a recess can be increased.

[0025] Furthermore, a method for producing a variant of the previously presented microfluidic receiving element is presented. The method comprises a step of applying the hydrophilic layer to at least part of the surface of the at least one recess. The above method further comprises a step of forming the hydrophobic layer on at least part of the surface of the recess. Such a production of the microfluidic receiving element offers the advantages of good fillability of the recess due to an adapted geometry of the recess and / or the advantages of minimized carryover during subsequent use of the receiving element.

[0026] According to one embodiment, the forming step may be performed before the applying step or after the applying step.

[0027] This method can be implemented, for example, in software or hardware, or in a hybrid form of software and hardware, for example, in a control unit. The approach presented here further creates a control unit configured to perform, control, and / or implement the steps of a variant of the method presented here in corresponding devices. This embodiment of the approach presented in the form of a control unit also allows the problem underlying the approach presented to be solved quickly and efficiently.

[0028] 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.

[0029] 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.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.

[0030] A machine-readable storage medium on which the previous computer program or computer program product is stored is also advantageous.

[0031] Examples of the approach presented here are shown in the drawings and explained in more detail in the following description. It shows:

[0032] Fig. 1 is a schematic cross-sectional view of a microfluidic device according to an embodiment;

[0033] Fig. 2a is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess;

[0034] Fig. 2b is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess;

[0035] Fig. 2c is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess;

[0036] Fig. 2d is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess;

[0037] Fig. 2e is a schematic cross-sectional view of an embodiment of a microfluidic receiving element with a recess; Fig. 3a is a schematic top view of an embodiment of a microfluidic receiving element with a recess;

[0038] Fig. 3b is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0039] Fig. 3c is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0040] Fig. 3d is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0041] Fig. 3e is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0042] Fig. 3f is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0043] Fig. 3g is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0044] Fig. 3h is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0045] Fig. 3i is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0046] Fig. 3j is a schematic plan view of an embodiment of a microfluidic receiving element with a recess;

[0047] Fig. 4 is a flow diagram of an embodiment of a method for producing a microfluidic receiving element; and

[0048] Fig. 5 shows a schematic representation of a control unit according to one exemplary embodiment. In the following description of advantageous exemplary embodiments of the present approach, 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.

[0049] Fig. 1 shows a schematic cross-sectional view of a microfluidic device 100 according to one embodiment. The device 100 is designed to process fluids, and thus, for example, substances dissolved in a fluid. For this purpose, the device 100 comprises a microfluidic receiving element 110, which in this embodiment is arranged on a flow cell 105. The receiving element 110 has a recess 115 for receiving an aqueous solution, i.e., a sample liquid.

[0050] In this exemplary embodiment, the receiving element 110 comprises, merely by way of example, in addition to the recess 115, a second recess 135, as well as, merely by way of example, a third recess 140, a fourth recess 142, a fifth recess 144 and a sixth recess 146, wherein all recesses 115, 135, 140, 142, 144, 146 are arranged in a plane of an upper side 130 of the receiving element 110, and wherein all recesses 115, 135, 140, 142, 144, 146 are identical to one another in shape and size.

[0051] The illustrated receiving element 110, or a similar receiving element, is an important component of microfluidic analysis systems. Small reaction chambers of the receiving element 110, i.e., the recesses 115, 135, 140, 142, 144, 146, can accommodate the fluids to be analyzed.

[0052] Fig. 2a shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element 110 with a recess 115. A surface 200 of the recess 115 has a hydrophilic layer 205. This hydrophilic layer 205 is arranged on the top side 130 of the receiving element 110 and in a partial region of the side wall 120 of the recess 115. The surface 200 of the recess 115 also has a hydrophobic layer 210. This hydrophobic layer 210 is arranged on a bottom 215 of the recess 115 and in a partial region of the side wall 120 of the recess 115.

[0053] The hydrophobic layer 210 has a larger surface area on the side wall 120 of the recess 115 than the hydrophilic layer 205.

[0054] A height hL of the hydrophilic layer 205 on the side wall 120 of the recess 115 is less than a height hB of the hydrophobic layer 210.

[0055] The height hB of the hydrophobic layer 210 is less than a height hA of the recess 115. The height hL of the hydrophilic layer 205 is also less than the height hA of the recess 115.

[0056] For the cavity to be filled with sample fluid, the chip surface may, for example, be sufficiently hydrophilic. This can be promoted or ensured by a non-selective, conformal layer. In such a case, many or all surfaces of the chip and the cavity may be hydrophilic.

[0057] In other words, Fig. 2a shows a schematic cross-section of a well indicating the depth of the well and the height of the hydrophobic coating.

[0058] Fig. 2b shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element 110 with a recess 115. The surface 200 of the recess 115 has a hydrophilic layer 205. This hydrophilic layer 205 is arranged on the top side 130 of the receiving element 110, on the side wall 120 of the recess 115, and between the bottom 215 of the recess 110 and a hydrophobic layer 210, which is arranged on the bottom 215 of the recess 115 above or on the hydrophilic layer 205 and in a partial region of the side wall 120 of the recess 115 above or on the hydrophilic layer 205. The hydrophilic layer 205 has a larger surface area on the side wall 120 of the recess 115 than the hydrophobic layer 210.

[0059] The height hL of the hydrophilic layer 205 on the side wall 120 of the recess 115 is greater than the height hB of the hydrophobic layer 210.

[0060] The height hB of the hydrophobic layer 210 is less than the height hA of the recess 115. The height hL of the hydrophilic layer 205 corresponds to the height hA of the recess 115.

[0061] In other words, Fig. 2b shows a variant of the microfluidic receiving element 110, wherein the hydrophobic layer is arranged on the hydrophilic layer.

[0062] Fig. 2c shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element 110 with a recess 115. The surface 200 of the recess 115 has a hydrophilic layer 205. This hydrophilic layer 205 is arranged on the top side 130 of the receiving element 110 and in a partial region of the side wall 120 of the recess 115.

[0063] The surface 200 of the recess 115 also has a hydrophobic layer 210. This hydrophobic layer 210 is arranged on the bottom 215 of the recess 115 and in a partial region of the side wall 120 of the recess 115.

[0064] The surface 200 of the recess 115 is exposed on the side wall 120 of the recess 115 in a free area 220 between the hydrophobic layer 210 and the hydrophilic layer 205.

[0065] The hydrophobic layer 210 has a larger surface area on the side wall 120 of the recess 115 than the hydrophilic layer 205 and a larger surface area than the free area 220. The hydrophilic layer 205 also has a larger surface area on the side wall 120 of the recess 115 than the free area 220.

[0066] The height hL of the hydrophilic layer 205 on the side wall 120 of the recess 115 is less than the height hB of the hydrophobic layer 210. A height hF of the free area 220 is less than the height hB of the hydrophobic layer 210 and also less than the height hL of the hydrophilic layer 205.

[0067] The height hB of the hydrophobic layer 210 is less than the height hA of the recess 115. The height hL of the hydrophilic layer 205 is also less than the height hA of the recess 115. The height hF of the free area 220 is also less than the height hA of the recess 115.

[0068] In other words, Fig. 2c shows a variant of the microfluidic receiving element 110, wherein parts of the well wall are not coated.

[0069] Fig. 2d shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element 110 with a recess 115. A reagent 225 for conducting an analytical reaction with a sample liquid is stored in the recess 115. A height hR of the reagent 225 is smaller than the height hA of the recess 115. The reagent 225 is arranged on the bottom 215 of the recess 115 and encloses a portion of the side wall 120 of the recess 115.

[0070] In other words, Fig. 2d shows a variant with a definition of the filling height of the reagent in the well with an assumed contact angle of the well side wall of 90 degrees.”

[0071] Fig. 2e shows a schematic cross-sectional view of an embodiment of a microfluidic receiving element 110 with a recess 115. The surface 200 of the recess 115 has a hydrophilic layer 205. This hydrophilic layer 205 is arranged on the top side 130 of the receiving element 110 and in a partial region of the side wall 120 of the recess 115. The surface 200 of the recess 115 also has a hydrophobic layer 210. This hydrophobic layer 210 is arranged on the bottom 215 of the recess 115 and in a partial region of the side wall 120 of the recess 115.

[0072] The hydrophobic layer 210 has a larger surface area on the side wall 120 of the recess 115 than the hydrophilic layer 205.

[0073] The height hL of the hydrophilic layer 205 on the side wall 120 of the recess 115 is less than the height hB of the hydrophobic layer 210.

[0074] The height hB of the hydrophobic layer 210 is less than the height hA of the recess 115. The height hL of the hydrophilic layer 205 is also less than the height hA of the recess 115.

[0075] The reagent 225 is aligned at, on, and / or above the hydrophobic layer 210 in a region of the bottom 215 of the recess 115, and at and / or above the hydrophobic layer 210 in a partial region of the sidewall 120. The reagent 225 repels the hydrophilic layer 205, creating a curvature of a phase interface of the reagent 225 on an upper side of the reagent 225.

[0076] The height hR of the reagent 225 is smaller than the height hA of the recess 115, but the height hR of the reagent 225 in a central region of the recess 115 is greater than the height hB of the hydrophobic layer 210. In an edge region of the recess 115 adjacent to the hydrophobic layer 210, the height hR of the reagent 225 is smaller than the height hB of the hydrophobic layer 210. This is due to the fact that the height hR of the reagent 225 is greater in the central region of the recess 115 than in the edge region of the recess 115 adjacent to the hydrophobic layer 210. In other words, the height hR of the reagent 225 decreases from the central region of the recess 115 to the edge region of the recess 115. In other words, Fig. 2e shows a schematic cross-section of a well in a variant of the microfluidic receiving element 110 with spotted reagent.

[0077] As a summary for the sub-figures of Fig. 2, it can be noted that the height hB, up to which the recess 115, i.e., the well wall, is hydrophobic, is variable, but hB is usually less than the height hA of the recess 115. If the height hB of the hydrophobic layer is too low—i.e., if hB is too small—the spotted reagent 225 illustrated in Figures 2d and 2e could come into contact with the hydrophilic layer 205, which could induce a capillary effect. In such a case, the reagent 225 could pull itself up the side wall 120 of the recess 115, which is to be avoided. If the height hB of the hydrophobic layer 210 is too high, for example, below an upper edge of the recess 115, i.e., if hB approximately corresponds to hA, filling of the recess 115 may be impeded. Ideally, the height hB of the hydrophobic layer 210 is slightly larger than a (later) filling height hR of the reagent 225.For example, hB can correspond to the filling height hR of the reagent 225 times 1.1.

[0078] The partial figures of Fig. 3 show “various advantageous corrugation geometries in plan view”.

[0079] In other words, the sub-figures of Fig. 3 show schematic top views of possible wells or variants of the microfluidic receiving element 110.

[0080] Fig. 3a shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115 has, at least partially, an angular geometry and / or shape in a plane of the upper side of the receiving element, i.e., a basic shape of the recess 115 is angular. In Fig. 3a, the recess 115 has six corners, thus representing a hexagon.

[0081] According to one embodiment, a silicon chip, alternatively called a Si chip, silicon chip, or in short, a chip, can comprise at least one well such that the wells, in a top view, or top view for short, can have at least one corner – that is, the wells are not round or slightly oval – and / or such that surface properties can be hydrophilic at least on part or a majority of the chip surface – that is, the contact angle of a water droplet on a surface is less than 90 degrees – and / or such that only a partial region of the well could be hydrophobic. Such a hydrophobic partial region of the well can, for example, be arranged near a well bottom (see Figs. 2a, 2b, 2c, and 2e).

[0082] For example, a square well design and / or a hydrophilic surface can promote or ensure favorable well filling. A hydrophobic layer in a portion of the well near the well bottom, where a reagent can be deposited during spotting, can prevent the reagent from experiencing capillary action, i.e., from being drawn up into a corner or corners of the well. This makes it less likely that the reagent will be carried over and / or washed out in a subsequent fluidics step (see Figure 2e).

[0083] Fig. 3b shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115 has at least partially an angular geometry and / or shape in the plane of the upper side of the receiving element, i.e., the basic shape of the recess 115 is angular. In Fig. 3b, the recess 115 has four corners, thus representing a quadrilateral.

[0084] Fig. 3c shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic shape, has, at least partially, an angular, in particular serrated, geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element. The recess 115 thus has a plurality of serrations in the edge region of the recess 115. Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 results.

[0085] Conventional round, elliptical, or oval wells, i.e., recesses, without at least partially square edges, may not be easy to fill with a liquid, especially an analyte, in a flow cell, especially with a flow parallel to the chip surface, because the liquid could flow around the outside of the recess instead of entering the recess (which would represent filling the recess). Failure to fill the recesses can result in the failure of a desired detection reaction. This can result in the failure of the respective well and possibly in misinterpretation of data and / or non-detection of a disease – in particular, a test result of the detection reaction can be falsely negative.Wells with a shape deviating from the round, (slightly) elliptical or (slightly) oval shape can, for example, have corners and / or at least areas with a (strongly) increased curvature - in particular with a small radius, for example a radius of less than 175 micrometers.

[0086] These corners can lead to an obstruction of the flow around the well due to the surface tension of the analyte, so that the probability of the liquid flowing into the well can be (significantly) increased. Filling the wells according to embodiments of the disclosed approach can thus be simplified compared to filling conventional round wells.

[0087] However, if the well sidewalls of a conventional well have a conventional hydrophilic surface, corners in the edge area of ​​the well can also lead to liquid located in the well (e.g., when a reagent is introduced, i.e., spotted, into the well) being drawn up into a corner of the recess by capillary action. In a subsequent fluidic step (e.g., during flushing and / or filling with the analyte), this liquid could be washed out and / or possibly carried over to another recess. Such carryover can lead to discharge and / or cross-contamination, for example, in adjacent wells.This, in turn, can lead to a chemical or biochemical reaction not occurring in a conventional well, for example, because a reactant is no longer present in the required amount and / or because an additional reactant—particularly the reactant of an adjacent well—is present, inhibiting, hindering, or preventing the reaction. Alternatively, an incorrect reaction could occur in a conventional well because a chemical other than the original one is also present in the well. All of this could lead to a malfunction of a conventional microfluidic device associated with the described conventional well—for example, to a false positive or false negative test result.

[0088] This means that simple filling and low carryover cannot traditionally be optimized simultaneously through simple geometry changes. A chip, i.e., a microfluidic device, according to one embodiment, and / or wells, i.e., recesses, according to one embodiment, can (in contrast) ideally be advantageously filled and (simultaneously) prevent, minimize, or reduce so-called carryover.

[0089] Fig. 3d shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic form, has, at least partially, an angular, in particular serrated, geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element. The recess 115 thus has a plurality of serrations in the edge region of the recess 115. Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 results.

[0090] Fig. 3e shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic shape, has, at least partially, an angular, in particular serrated, geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element. The recess 115 thus has a plurality of serrations in the edge region of the recess 115. Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 results.

[0091] Fig. 3f shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic form, has at least partially an angular geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element. The recess 115 thus has a plurality of angular shapes in the edge region of the recess 115. Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 results.

[0092] Fig. 3g shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic shape, has, at least partially, an angular, in particular serrated, geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element. The recess 115 thus has a plurality of serrations in the edge region of the recess 115. Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 results.

[0093] Fig. 3h shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic shape, has at least partially an angular, in particular a serrated, geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element. Due to the underlying circular and / or cylindrical geometry of the recess 115, a shape of the recess 115 results. Fig. 3i shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic shape, has at least partially an angular, in particular a segmented Archimedean spiral, geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element.Due to the underlying circular and / or cylindrical geometry of the recess 115, a segmented Archimedean spiral shape of the recess 115 results.

[0094] Fig. 3j shows a schematic top view of an embodiment of a microfluidic receiving element 110 with a recess 115. The recess 115, which is round in its basic shape, has, at least partially, an angular, in particular a segmented Archimedean spiral, geometry and / or shape in an edge region of the recess 115 in the plane of the upper side of the receiving element. Due to the underlying circular and / or cylindrical geometry of the recess 115, a segmented Archimedean spiral shape of the recess 115 results.

[0095] Fig. 4 shows a flowchart of an embodiment of a method 400 for producing a microfluidic receiving element. According to one embodiment, an uncoated but (already) structured microfluidic device—also referred to as a wafer—can be provided at the beginning of the method. This means that the wells can already be defined on the wafer, i.e., in a surface of a substrate of the receiving element. The recess accordingly has at least partially an angular geometry and / or shape in the plane of the upper side of the receiving element.

[0096] The method 400 comprises a step 410 of applying a hydrophilic layer to at least a portion of the surface of the at least one recess.

[0097] The method 400 comprises a step 420 of forming the hydrophobic layer on at least part of the surface of the recess. The forming step 420 can be performed, in particular, before the applying step 410 or after the applying step 410.

[0098] According to one embodiment, in a method 400 for "spotting a hydrophobic layer," in step 410 of application, the wafers can be completely, homogeneously, and conformally coated with a hydrophilic layer and / or surface modification, for example, as is conventional from a gas phase or wet-chemically. According to this embodiment, in step 420 of formation, a liquid can be spotted, i.e., introduced, into at least one well, in particular a liquid that has hydrophobic properties after drying. By spotting a specific amount of the liquid, the height of the hydrophobic layer in the well can be easily adjusted.

[0099] According to an additional embodiment, in a method 400 for "structuring a hydrophobic layer and for (subsequent) selective hydrophilic coating," in step 420 of forming the wafer, the wafers can be completely, homogeneously, and conformally coated with a hydrophobic layer and / or surface modification, for example, as is conventional from a gas phase or wet-chemically. According to this embodiment, a protective layer can then be introduced into the wells, specifically at the locations where the hydrophobic surface properties are later to be retained. This can be done, for example, by spotting a protective layer, in particular a protective resist. According to this embodiment, unprotected areas of the hydrophobic layer can then be removed, specifically by an oxygen plasma, by a (directed) Ar plasma, wet-chemically, or by UV exposure.According to this exemplary embodiment of method 400, the wafer can then be selectively coated with a hydrophilic layer, for example, from the gas phase or wet-chemically. The selectivity of such a layer is conventionally present because conventional layers (based on trichlorosilanes or trimethoxy groups) can dock, in particular, onto OH groups of a substrate to be coated and bond covalently there. If the OH groups are saturated, for example with another, in particular a hydrophobic, molecule, or if no OH groups are present (for example on the protective resist), no layer is likely to form there, but presumably only on a previously cleaned chip surface. According to this exemplary embodiment, the protective layer can subsequently be removed; for example, the protective resist can be dissolved in a suitable solvent, for example acetone.

[0100] According to one embodiment, in step 410 of application and / or in step 420 of formation, the surface of the chips can be coated with an organosilanol or organosilanols functioning as a hydrophobic layer and / or hydrophilic layer. According to one embodiment, these organosilanols can have an organic functional group and three hydrolyzable substituents, for example, trimethoxysilanes or trichlorosilanes. By means of the hydrolyzable substituents, for example, the functional organic group can be covalently bonded to a surface. According to embodiments, possible hydrophilic functional groups can be, in particular, polyethylene glycol (PEG) groups or epoxy groups.According to embodiments, possible hydrophobic functional groups can be (fluoro)alkylsilanes, in particular heptadecafluorodecyltrimethoxysilanes, (heptafluoroisopropoxy)propyltrichlorosilanes, octadecyldimethylchlorosilanes, octadecyltrichlorosilanes, octyldimethylchlorosilanes, dimethyldichlorosilanes, butyldimethylchlorosilanes, or trimethylchlorosilanes. According to another embodiment, a possible hydrophobic surface coating can be hexamethyldisilazane (HMDS).

[0101] According to embodiments, the hydrophilic layer and / or the hydrophobic layer can have a layer thickness of one monolayer or a few monolayers - in particular in the case of full-surface deposition from the gas phase or wet-chemically - up to several micrometers - in particular when drying a spotted chemical.

[0102] According to one embodiment, by carrying out the aforementioned step 410 or the aforementioned steps 410, 420, the microfluidic receiving element can be produced in particular including well wall properties.

[0103] Fig. 5 shows a schematic representation of a control unit 500 according to one exemplary embodiment. The control unit 500 is configured to execute and / or control step 410 or steps 410, 420 of the method 400 in a corresponding unit 510 or in corresponding units 510, 520.

[0104] According to one embodiment, the approach presented here can be demonstrated by inspecting the chips using surface analysis, in particular XPS, and / or by contact angle measurements on the chip surface.

[0105] The approach presented here can alternatively be referred to as a “microfluidic Si chip with easily fillable cavities and minimized carryover”.

[0106] If an embodiment comprises an “and / or” link between a first feature and a second feature, this is to be read as meaning that the embodiment according to one embodiment has both the first feature and the second feature and according to another embodiment has either only the first feature or only the second feature.

Claims

Claims 1 . A microfluidic receiving element (110) for a microfluidic device (100) for processing fluids, wherein at least one recess (115) for receiving a sample liquid is arranged in a plane of a top side (130) of the receiving element (110), wherein a surface (200) of the recess (115) at least partially comprises a hydrophilic layer (205) and wherein the surface (200) of the recess (115) at least partially comprises a hydrophobic layer (210) 2. Microfluidic receiving element (110) according to claim 1, wherein the recess (115) in the plane of the upper side (130) of the receiving element (110) has at least partially an angular geometry and / or shape.

3. Microfluidic receiving element (110) according to one of the preceding claims, wherein the hydrophobic layer (210) is arranged on a bottom (215) of the recess (115) and / or at least on a partial region of at least one side wall (120) of the recess (115).

4. Microfluidic receiving element (110) according to one of the preceding claims, wherein the surface (200) of the recess (115) is exposed on the side wall (120) of the recess (115) in a free area (220) between the hydrophobic layer (210) and the hydrophilic layer (205).

5. Microfluidic receiving element (110) according to one of the preceding claims, wherein the hydrophobic layer (210) on the side wall (120) of the recess (115) has a larger surface area than the hydrophilic layer (205).

6. Microfluidic receiving element (110) according to one of the preceding claims, wherein a height (hB) of the hydrophobic layer (210) is less than a height (hA) of the recess (115) and / or wherein the height (hB) of the hydrophobic layer (210) is greater than a height (hL) of the hydrophilic layer (205) on the side wall (120) of the recess (115).

7. Microfluidic receiving element (110) according to one of the preceding claims, wherein the hydrophilic layer (205) is further arranged on the upper side (130) of the receiving element (110) and / or at least on a partial region of the side wall (120) and / or between the hydrophobic layer (210) and the bottom (215) of the recess (115).

8. Microfluidic receiving element (110) according to one of the preceding claims, wherein a reagent (225) for carrying out an analytical reaction with the sample liquid is disposed in the recess (115).

9. Microfluidic receiving element (110) according to one of the preceding claims, wherein at least one further recess (135) for receiving a sample liquid is arranged in the plane of the upper side (130) of the receiving element (110), wherein a surface of the further recess (135) at least partially comprises the hydrophilic layer (205) or a further hydrophilic layer and at least partially comprises the hydrophobic layer (210) or a further hydrophobic layer.

10. Microfluidic device (100) for processing fluids with the microfluidic receiving element (110) according to one of the preceding claims.

11. A method (400) for producing a microfluidic receiving element according to any one of claims 1 to 9, wherein the method (400) comprises the following step: - applying (410) a hydrophilic layer to at least a part of the surface of the at least one recess; and Forming (420) a hydrophobic layer on at least a portion of the surface of the recess.

12. The method (400) according to claim 11, wherein the step (420) of forming is performed before the step (410) of applying or after the step (410) of applying.

13. Control device (500) which is configured to carry out and / or control the step (410) or the steps (410, 420) of the method (400) according to one of the preceding claims in a corresponding unit (510) or in corresponding units (510, 520).

14. Computer program configured to execute and / or control the step (410) or the steps (410, 420) of the method (400) according to one of the preceding claims.

15. A machine-readable storage medium on which the computer program according to claim 14 is stored.

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